Lyme Disease: Laboratory Support of Diagnosis and Management

This Clinical Focus provides information about laboratory tests related to Lyme disease.

Clinical Focus

Lyme Disease

Laboratory Support of Diagnosis and Management

Contents:

Clinical background

Table 1. Lyme Disease: Stages, Symptoms, and Recommended Laboratory Testing

Individuals suitable for testing

Test availability

Table 2. Tests Available for Diagnosis and Management of Lyme Disease

Test selection and interpretation

References

Clinical background [return to contents]

Lyme disease or Lyme borreliosis is by far the most common tick-borne disease in the United States. It is caused by the bacterium Borrelia burgdorferi and transmitted from the deer tick (Ixodes scapularis or Ixodes pacificus). In 2023, approximately 90,000 cases of Lyme disease were reported to the CDC by healthcare providers¹but, based on insurance claims data, the annual number of patients diagnosed and treated could be as high as 476,000 per year^.2

Lyme disease cases are most frequently reported from the upper midwestern, northeastern, and Mid-Atlantic states.³ However, cases are also reported from Northern California, Oregon, and Washington. Lyme disease is most common among children and middle-aged adults.⁴

The clinical presentation of Lyme disease is categorized as 1 of 3 stages: early localized, early disseminated, and late (Table 1).^3,5-7 In 70% to 80% of infected persons, early localized disease is characterized by erythema migrans (EM), a round skin lesion at least 4 cm to 5 cm in diameter that may appear in a “bulls-eye” pattern and expand up to 30 cm across.³ In the absence of EM, the differential diagnosis may include other tick-borne diseases such as hard tick relapsing fever (Borrelia miyamotoi disease), which is often misdiagnosed as Lyme disease owing to overlapping symptoms.⁸

Table 1. Lyme Disease: Stages, Symptoms, and Recommended Laboratory Testing [return to contents]

Stage of disease3,5	Symptom onset³	Symptoms3	Laboratory testing3,7
Early localized (acute phase)	3-30 days after tick bite	EM Fever, myalgia, headache, nausea, fatigue	If EM is identified in a patient where Lyme disease is endemic, serologic testing is not recommended (ie, clinical diagnosis of Lyme is recommended) STTT or MTTT may be considered (weakly recommended) for patients with 1 or more skin lesions suggestive of but atypical for EM; however, serologic testing during the acute phase of infection is less sensitive and specific than testing at later stages of infection
Early disseminated	3-12 weeks after tick bite	Dermatologic: multiple EM rashes that are distant from bite Neurologic: LNB – common symptoms include Bell’s palsy, lymphocytic meningitis, painful radiculoneuritis (1 or more dermatomes), and others such as painful peripheral motor and sensory neuropathy (mononeuritis multiplex) and intracranial hypertension (rare) Cardiac: Lyme carditis leading to conduction abnormalities such as AV node block; can be fatal (rare) Rheumatologic: transient and/or migratory arthritis; effusion in 1 or more joints, often large joints; Baker’s cysts; migratory pain in tendons, bursae, muscle, and bones	When assessing for possible LNB affecting either the PNS or CNS, STTT or MTTT, serum is recommended If LNB or 1 or more acute symptoms (eg, meningitis, painful radiculoneuritis) of LNB is suspected, guideline recommendations include obtaining simultaneous samples of CSF and serum for measuring CSF:serum antibody index STTT or MTTT is recommended when assessing for rheumatologic symptoms of Lyme disease; PCR is recommended in seropositive patients
Late-stage	Months to years after tick bite	Patients may not have a history of EM, however, may present with sensory axonal polyneuropathy, encephalomyelitis (rare), or mononeuropathy Cognitive deficits, personality changes, extreme irritability, and depression Lyme arthritis Bluish red rash (acrodermatitis chronica atrophicans) in women	STTT or MTTT is recommended with IgG only considered >30 days after symptom onset

CNS, central nervous system; CSF, cerebrospinal fluid; EM, erythema migrans; LNB, Lyme neuroborreliosis; MTTT, modified 2-tiered testing; PCR, polymerase chain reaction; PNS, peripheral nervous system; STTT, standard 2-tiered testing.

The first sign of early disseminated disease is often additional smaller skin lesions that may develop if Lyme disease is untreated; however, a recognized skin lesion does not always occur. Extracutaneous involvement in early disseminated disease can include cardiac, rheumatologic, and/or neurologic manifestations (Table 1).^3,5-7 About 10% to 15% of patients with untreated Lyme disease will develop Lyme neuroborreliosis (LNB).⁹ Lyme arthritis may also occur during late-stage disease and is the most common manifestation of Lyme disease months after initial tick exposure.¹⁰ Left untreated, Lyme arthritis usually affects the knees over a period of several years.¹⁰

If initiated in the early stages of Lyme disease, treatment with appropriate antibiotics is usually effective.⁷ Prophylaxis or serologic testing after a tick bite is usually not indicated in areas where less than 20% of ticks are infected; however, in areas where infected ticks are endemic, laboratory testing, including tick identification, is recommended.⁷

This Clinical Focus provides information on appropriate test selection and interpretation in patients with suspected Lyme disease. The information in the text and tables is provided for informational purposes only and is not intended as medical advice. Test selection and interpretation, diagnosis, and patient management decisions should be based on the physician’s education, clinical expertise, and assessment of the patient.

Individuals suitable for testing [return to contents]

Symptomatic (Table 1) individuals with a history of exposure to a tick-endemic area

Test availability [return to contents]

Laboratory tests that can help confirm the clinical diagnosis of Lyme disease include tick identification, various serologic techniques and polymerase chain reaction (PCR)-based assays (Table 2). Panel components may be ordered individually.

Table 2. Tests Available for Diagnosis and Management of Lyme Disease [return to contents]

Test code	Assaya (component test code)	Method	Clinical use
39209	Borrelia burgdorferi DNA, Qualitative Real-Time PCR, Miscellaneous^b,c	Real-time PCR	Diagnose Lyme disease using whole blood, synovial fluid, or CSF
39684	Borrelia miyamotoi Antibody (IgG, IgM), Immunoassay^b	Immunoassay	Differentially diagnose B miyamotoi disease vs Lyme disease
93795	Borrelia miyamotoi DNA, Qualitative Real-Time PCR, Miscellaneous^b	Real-time PCR	Confirm diagnosis of B miyamotoi disease
15777	Borrelia Species DNA, Qualitative Real-Time PCR, Miscellaneous^b	Real-time PCR	Detect Borrelia spp DNA in whole blood, synovial fluid, or CSF
15510	Borrelia Species DNA, Qualitative Real-Time PCR, Tick^b	Real-time PCR	Detect B burgdorferi in tick to assess risk of Lyme disease
39219	Borrelia Species DNA, Real-Time PCR, With Reflexes, Blood^c,d	Real-time PCR	Detect Borrelia spp DNA; diagnose Lyme disease or B miyamotoi disease in whole blood
39218	Borrelia Species DNA, Real-Time PCR, With Reflexes, Synovial Fluid/CSF^c,d	Real-time PCR	Detect Borrelia spp DNA; diagnose Lyme disease or B miyamotoi disease in synovial fluid or CSF
6646	Lyme Disease Ab With Reflex to Blot (IgG, IgM)^d	Immunoassay	Diagnose Lyme disease by standard 2-tiered test
39733	Lyme Disease Antibody With Reflex to Immunoassay (IgG, IgM) (MTTT)^d Includes reflex to Lyme disease supplemental antibodies (IgG, IgM) if Lyme disease antibody is positive or equivocal.	Immunoassay	Diagnose Lyme disease by modified 2-tiered test
34194	Lyme Disease Antibody Index for CNS Infection	ELISA; Nephelometry	Diagnose Lyme neuroborreliosis
8593	Lyme Disease Antibodies (IgG, IgM), Immunoblot	Immunoblot	Diagnose Lyme disease when ELISA results are positive or equivocal
29477	Lyme Disease Antibody (IgG), Immunoblot	Immunoblot
94322	Tick-borne Disease, Acute Molecular Panel Includes Anaplasma phagocytophilum (17320), Babesia microti (37314), Borrelia miyamotoi (93795), Ehrlichia chaffeensis (11353), and Lyme disease Borrelia spp (15777).	Real-time PCR	Diagnose tick-borne diseases when selecting tests for individual pathogens is challenging owing to overlapping geographic distributions and clinical presentations of illness; especially useful to diagnose mixed infections
16220	Tick-borne Disease, Antibody Panel With Reflexes^b,d Includes Lyme disease Ab with reflex to immunoassay (IgG, IgM, 39733) and A phagocytophilum antibodies (IgG and IgM, 16189); B microti antibodies (IgG and IgM, 16194); and E chaffeensis (IgG and IgM, 16197) with reflexes to titers.	IFA	Diagnose tick-borne diseases when selecting tests for individual pathogens is challenging owing to substantial clinical overlap and coinfection
90558	Tick ID With Reflex to Lyme Disease DNA, Real-Time PCR, Tick^d	Microscopy; reflex to PCR	Identify tick and B burgdorferi to assess risk of tick-borne disease and assist with differential diagnosis

CSF, cerebrospinal fluid; ELISA, enzyme-linked immunosorbent assay; IFA, immunofluorescence assay; PCR, polymerase chain reaction.
a	Panel components may be ordered individually.
b	This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the US Food and Drug Administration. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.
c	Please refer to the Quest Test Directory for your service area for test availability. TestDirectory.QuestDiagnostics.com/Test/Home
d	Reflex tests are performed at an additional charge and are associated with an additional CPT® code(s).

Test selection and interpretation [return to contents]

A timeline of tick exposure in a tick-endemic area and symptoms of Lyme disease guide appropriate test selection (Table 1).^3,5-7 Guideline recommendations include testing for IgM and/or IgG antibodies using either standard 2-tiered testing (STTT, test code 6646) or modified 2-tiered testing (MTTT, test code 39733)^6,7,11; in MTTT, second-tier testing is performed by a second enzyme immunoassay instead of a Western blot. MTTT detects up to 30% more cases compared to STTT in patients with early Lyme disease.^12,13 The sections below outline appropriate test selection based on the stage of disease along with characteristic test results.

Early localized Lyme disease

Diagnosis of early localized Lyme disease can sometimes be made on the basis of EM alone without laboratory testing.³ Importantly, serologic testing during the acute phase of Lyme disease is less sensitive than at later stages of disease.⁶ When testing is done too soon (≤14 days) following infection, negative or equivocal results may occur due to the time needed for the immune system to develop a serologic response.⁶ Positive or repeat testing (test codes 29477, 8593) on another sample collected in 7 to 14 days is recommened.⁶ Serologic testing (MTTT or STTT) may also be considered in patients with 1 or more skin lesions suggestive of, but atypical for, EM.⁷

If first-tier testing performed 14 days after suspected infection is negative, then second-tier testing is not required.⁶ If first-tier testing is positive or equivocal, then second-tier testing is required.⁶ For samples collected from patients with symptoms lasting 30 days or less, positive IgM is consistent with infection regardless of IgG seropositivity.⁶

Early disseminated Lyme disease

Two-tiered testing is recommended when clinical findings are suggestive of early disseminated Lyme disease (Table 1).^3,5-7 For specimens collected at 2 to 4 weeks after onset of symptoms, 2-tiered testing that is positive for IgM and negative for IgG indicates early infection, unless obtained on a specimen collected more than 1 month after onset of symptoms.⁶ If the specimen was collected more than 1 month after onset of symptoms, a positive IgM finding is more likely to represent a false-positive result unless IgG is also positive; vaccination or other diseases may also cause false-positive results.⁶ A positive IgG result by 2-tiered testing is required to confirm the diagnosis of early disseminated Lyme disease but it does not differentiate between active and past B burgdorferi infection.^3,14

A diagnosis of LNB involving either the peripheral nervous system or central nervous system (CNS) can be supported if Borrelia antibody or DNA are detected in serum or cerebrospinal fluid (CSF); however, serum antibody testing is recommended over PCR due to low clinical sensitivity (38%).^7,15 If LNB involving the CNS is suspected and CSF testing is performed, a validated laboratory method for the determination of the CSF:serum antibody index using simultaneously obtained CSF and serum samples is recommended.⁷ The antibody levels in the CSF that are compared to control levels (ie, serum antibody or albumin) in the CSF:serum antibody index can be measured by enzyme-linked immunosorbent assay (ELISA) or nephelometry (test code 34194); an elevated antibody index strongly supports a diagnosis of LNB.¹⁶

Negative serology results may indicate lack of infection or lack of seroconversion, which may occur if samples are collected too early after disease onset or when early antibiotic therapy blunts the antibody response.⁶ PCR-based assays (test codes 94322, 39209, 15777, 39219, 39218, 15510, 90558) can be useful in the workup of B burgdorferi infection if seroconversion has not yet occurred; these assays, however, are limited by low clinical sensitivity (18%).¹⁷ Untreated patients who continue to be symptomatic for months or years but are IgG-negative are unlikely to have Lyme disease, and a differential diagnosis should be considered.⁷

Late-stage Lyme disease

In patients with suspected Lyme disease that has been left untreated for months to years after a tick bite, symptoms that are characteristic of late-stage disease such as Lyme arthritis or Lyme LNB can help guide diagnostic test selection. Detection of Borrelia DNA in synovial fluid, commonly from the knees, supports the diagnosis of Lyme arthritis (sensitivity, 78%; specificity, 100%).^10,17

Differential diagnosis

In addition to clinical presentation and microscopy, hard-tick relapsing fever (Borrelia miyamotoi disease) (HTRF [BMD]) can be distinguished from Lyme disease by serology (test code 39684) and molecular testing.³ Negative serology results do not rule out HTRF (BMD) infection and may be due to testing prior to seroconversion during the acute phase of infection.¹⁸ PCR amplification of B miyamotoi DNA (test code 93795) is part of an acute molecular panel of tests (94322) used to confirm a presumptive diagnosis of HTRF (BMD).

See Tick-borne Diseases: Laboratory Support of Diagnosis and Management for more details on HTRF (BMD) and information on differential diagnoses of other tick-borne diseases.

References [return to contents]

Lyme disease surveillance data. Centers for Disease Control and Prevention. Updated February 11, 2025. Accessed December 15, 2025. https://www.cdc.gov/lyme/data-research/facts-stats/surveillance-data-1.html
Kugeler KJ, Schwartz AM, Delorey MJ, et al. Estimating the frequency of Lyme disease diagnoses, United States, 2010-2018. Emerg Infect Dis. 2021;27(2):616-619. doi:10.3201/eid2702.202731
Tickborne diseases of the United States. A Reference Manual for Health Care Providers, 6th ed. Centers for Disease Control and Prevention; 2022. Accessed December 23, 2025 https://www.cdc.gov/ticks/media/pdfs/2025/03/tickborne-diseases-manual-508.pdf?CDC_AAref_Val=https://www.cdc.gov/ticks/tickbornediseases/TickborneDiseases-P.pdf.
Shapiro ED. Clinical practice: Lyme disease. N Engl J Med. 2014;370(18):1724-1731. doi:10.1056/NEJMcp1314325
Skar GL, Blum MA, Simonsen, KA. Lyme Disease In: StatPearls [Internet]. StatPearls Publishing; 2024. Updated October 1, 2024. Accessed December 15, 2025 https://www.ncbi.nlm.nih.gov/books/NBK431066/.
Suggested reporting language, interpretation and guidance for Lyme disease serologic test results (April 2024). Association of Public Health Laboratories. Updated April 2024. Accessed December 15, 2025. https://www.aphl.org/aboutAPHL/publications/Documents/ID-2024-Lyme-Disease-Serologic-Testing-Reporting.pdf
Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical practice guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme disease. Clin Infect Dis. 2021;72(1):e1-e48. doi:10.1093/cid/ciaa1215
Telford SR, Goethert HK, Molloy PJ, et al. Borrelia miyamotoi disease: neither Lyme disease nor relapsing fever. Clin Lab Med. 2015;35(4):867-882. doi:10.1016/j.cll.2015.08.002
Hildenbrand P, Craven DE, Jones R, et al. Lyme neuroborreliosis: manifestations of a rapidly emerging zoonosis. Am J Neuroradiol. 2009;30(6):1079-1087. doi:10.3174/ajnr.A1579
Steere AC. Treatment of Lyme arthritis. J Rheumatol. 2019;46(8):871-873. doi:10.3899/jrheum.190320
Mead P, Petersen J, Hinckley A. Updated CDC recommendation for serologic diagnosis of Lyme disease. MMWR Morb Mortal Wkly Rep. 2019;68(32):703. doi:10.15585/mmwr.mm6832a4
B. burgdorferi IgG/IgM Test System. [Package insert]. ZEUS Scientific; 2020.
Branda JA, Body BA, Boyle J, et al. Advances in serodiagnostic testing for Lyme disease are at hand. Clin Infect Dis. 2017;66(7):1133-1139. doi:10.1093/cid/cix943
Kalish RA, McHugh G, Granquist J, et al. Persistence of immunoglobulin M or immunoglobulin G antibody responses to Borrelia burgdorferi 10–20 years after active Lyme disease. Clin Infect Dis. 2001;33(6):780-785. doi:10.1086/322669
Nocton JJ, Bloom BJ, Rutledge BJ, et al. Detection of Borrelia burgdorferi DNA by polymerase chain reaction in cerebrospinal fluid in Lyme neuroborreliosis. J Infect Dis. 1996;174(3):623-627. doi:10.1093/infdis/174.3.623
Blanc F, Jaulhac B, Fleury M, et al. Relevance of the antibody index to diagnose Lyme neuroborreliosis among seropositive patients. Neurology. 2007;69(10):953-958. doi:10.1212/01.wnl.0000269672.17807.e0
Aguero-Rosenfeld ME, Wang G, Schwartz I, et al. Diagnosis of Lyme borreliosis. Clin Microbiol Rev. 2005;18(3):484-509. doi:10.1128/CMR.18.3.484-509.2005
Sudhindra P, Wang G, Schriefer ME, et al. Insights into Borrelia miyamotoi infection from an untreated case demonstrating relapsing fever, monocytosis and a positive C6 Lyme serology. Diagn Microbiol Infect Dis. 2016;86(1):93-96. doi:10.1016/j.diagmicrobio.2016.06.015

Content reviewed 1/2026

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This Clinical Focus provides information about laboratory tests related to Lyme disease.

Test Guide List

Lyme Disease: Laboratory Support of Diagnosis and Management

Clinical Focus

Lyme Disease

Laboratory Support of Diagnosis and Management

Contents:

Clinical background

Table 1. Lyme Disease: Stages, Symptoms, and Recommended Laboratory Testing

Individuals suitable for testing

Test availability

Table 2. Tests Available for Diagnosis and Management of Lyme Disease

Test selection and interpretation

References

Clinical background [return to contents]

Table 1. Lyme Disease: Stages, Symptoms, and Recommended Laboratory Testing [return to contents]

Stage of disease3,5	Symptom onset³	Symptoms3	Laboratory testing3,7
Early localized (acute phase)	3-30 days after tick bite	EM Fever, myalgia, headache, nausea, fatigue	If EM is identified in a patient where Lyme disease is endemic, serologic testing is not recommended (ie, clinical diagnosis of Lyme is recommended) STTT or MTTT may be considered (weakly recommended) for patients with 1 or more skin lesions suggestive of but atypical for EM; however, serologic testing during the acute phase of infection is less sensitive and specific than testing at later stages of infection
Early disseminated	3-12 weeks after tick bite	Dermatologic: multiple EM rashes that are distant from bite Neurologic: LNB – common symptoms include Bell’s palsy, lymphocytic meningitis, painful radiculoneuritis (1 or more dermatomes), and others such as painful peripheral motor and sensory neuropathy (mononeuritis multiplex) and intracranial hypertension (rare) Cardiac: Lyme carditis leading to conduction abnormalities such as AV node block; can be fatal (rare) Rheumatologic: transient and/or migratory arthritis; effusion in 1 or more joints, often large joints; Baker’s cysts; migratory pain in tendons, bursae, muscle, and bones	When assessing for possible LNB affecting either the PNS or CNS, STTT or MTTT, serum is recommended If LNB or 1 or more acute symptoms (eg, meningitis, painful radiculoneuritis) of LNB is suspected, guideline recommendations include obtaining simultaneous samples of CSF and serum for measuring CSF:serum antibody index STTT or MTTT is recommended when assessing for rheumatologic symptoms of Lyme disease; PCR is recommended in seropositive patients
Late-stage	Months to years after tick bite	Patients may not have a history of EM, however, may present with sensory axonal polyneuropathy, encephalomyelitis (rare), or mononeuropathy Cognitive deficits, personality changes, extreme irritability, and depression Lyme arthritis Bluish red rash (acrodermatitis chronica atrophicans) in women	STTT or MTTT is recommended with IgG only considered >30 days after symptom onset

Individuals suitable for testing [return to contents]

Symptomatic (Table 1) individuals with a history of exposure to a tick-endemic area

Test availability [return to contents]

Table 2. Tests Available for Diagnosis and Management of Lyme Disease [return to contents]

Test code	Assaya (component test code)	Method	Clinical use
39209	Borrelia burgdorferi DNA, Qualitative Real-Time PCR, Miscellaneous^b,c	Real-time PCR	Diagnose Lyme disease using whole blood, synovial fluid, or CSF
39684	Borrelia miyamotoi Antibody (IgG, IgM), Immunoassay^b	Immunoassay	Differentially diagnose B miyamotoi disease vs Lyme disease
93795	Borrelia miyamotoi DNA, Qualitative Real-Time PCR, Miscellaneous^b	Real-time PCR	Confirm diagnosis of B miyamotoi disease
15777	Borrelia Species DNA, Qualitative Real-Time PCR, Miscellaneous^b	Real-time PCR	Detect Borrelia spp DNA in whole blood, synovial fluid, or CSF
15510	Borrelia Species DNA, Qualitative Real-Time PCR, Tick^b	Real-time PCR	Detect B burgdorferi in tick to assess risk of Lyme disease
39219	Borrelia Species DNA, Real-Time PCR, With Reflexes, Blood^c,d	Real-time PCR	Detect Borrelia spp DNA; diagnose Lyme disease or B miyamotoi disease in whole blood
39218	Borrelia Species DNA, Real-Time PCR, With Reflexes, Synovial Fluid/CSF^c,d	Real-time PCR	Detect Borrelia spp DNA; diagnose Lyme disease or B miyamotoi disease in synovial fluid or CSF
6646	Lyme Disease Ab With Reflex to Blot (IgG, IgM)^d	Immunoassay	Diagnose Lyme disease by standard 2-tiered test
39733	Lyme Disease Antibody With Reflex to Immunoassay (IgG, IgM) (MTTT)^d Includes reflex to Lyme disease supplemental antibodies (IgG, IgM) if Lyme disease antibody is positive or equivocal.	Immunoassay	Diagnose Lyme disease by modified 2-tiered test
34194	Lyme Disease Antibody Index for CNS Infection	ELISA; Nephelometry	Diagnose Lyme neuroborreliosis
8593	Lyme Disease Antibodies (IgG, IgM), Immunoblot	Immunoblot	Diagnose Lyme disease when ELISA results are positive or equivocal
29477	Lyme Disease Antibody (IgG), Immunoblot	Immunoblot
94322	Tick-borne Disease, Acute Molecular Panel Includes Anaplasma phagocytophilum (17320), Babesia microti (37314), Borrelia miyamotoi (93795), Ehrlichia chaffeensis (11353), and Lyme disease Borrelia spp (15777).	Real-time PCR	Diagnose tick-borne diseases when selecting tests for individual pathogens is challenging owing to overlapping geographic distributions and clinical presentations of illness; especially useful to diagnose mixed infections
16220	Tick-borne Disease, Antibody Panel With Reflexes^b,d Includes Lyme disease Ab with reflex to immunoassay (IgG, IgM, 39733) and A phagocytophilum antibodies (IgG and IgM, 16189); B microti antibodies (IgG and IgM, 16194); and E chaffeensis (IgG and IgM, 16197) with reflexes to titers.	IFA	Diagnose tick-borne diseases when selecting tests for individual pathogens is challenging owing to substantial clinical overlap and coinfection
90558	Tick ID With Reflex to Lyme Disease DNA, Real-Time PCR, Tick^d	Microscopy; reflex to PCR	Identify tick and B burgdorferi to assess risk of tick-borne disease and assist with differential diagnosis

CSF, cerebrospinal fluid; ELISA, enzyme-linked immunosorbent assay; IFA, immunofluorescence assay; PCR, polymerase chain reaction.
a	Panel components may be ordered individually.
b	This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the US Food and Drug Administration. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.
c	Please refer to the Quest Test Directory for your service area for test availability. TestDirectory.QuestDiagnostics.com/Test/Home
d	Reflex tests are performed at an additional charge and are associated with an additional CPT® code(s).

Test selection and interpretation [return to contents]

Early localized Lyme disease

Early disseminated Lyme disease

Late-stage Lyme disease

Differential diagnosis

See Tick-borne Diseases: Laboratory Support of Diagnosis and Management for more details on HTRF (BMD) and information on differential diagnoses of other tick-borne diseases.

References [return to contents]

Lyme disease surveillance data. Centers for Disease Control and Prevention. Updated February 11, 2025. Accessed December 15, 2025. https://www.cdc.gov/lyme/data-research/facts-stats/surveillance-data-1.html
Kugeler KJ, Schwartz AM, Delorey MJ, et al. Estimating the frequency of Lyme disease diagnoses, United States, 2010-2018. Emerg Infect Dis. 2021;27(2):616-619. doi:10.3201/eid2702.202731
Tickborne diseases of the United States. A Reference Manual for Health Care Providers, 6th ed. Centers for Disease Control and Prevention; 2022. Accessed December 23, 2025 https://www.cdc.gov/ticks/media/pdfs/2025/03/tickborne-diseases-manual-508.pdf?CDC_AAref_Val=https://www.cdc.gov/ticks/tickbornediseases/TickborneDiseases-P.pdf.
Shapiro ED. Clinical practice: Lyme disease. N Engl J Med. 2014;370(18):1724-1731. doi:10.1056/NEJMcp1314325
Skar GL, Blum MA, Simonsen, KA. Lyme Disease In: StatPearls [Internet]. StatPearls Publishing; 2024. Updated October 1, 2024. Accessed December 15, 2025 https://www.ncbi.nlm.nih.gov/books/NBK431066/.
Suggested reporting language, interpretation and guidance for Lyme disease serologic test results (April 2024). Association of Public Health Laboratories. Updated April 2024. Accessed December 15, 2025. https://www.aphl.org/aboutAPHL/publications/Documents/ID-2024-Lyme-Disease-Serologic-Testing-Reporting.pdf
Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical practice guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme disease. Clin Infect Dis. 2021;72(1):e1-e48. doi:10.1093/cid/ciaa1215
Telford SR, Goethert HK, Molloy PJ, et al. Borrelia miyamotoi disease: neither Lyme disease nor relapsing fever. Clin Lab Med. 2015;35(4):867-882. doi:10.1016/j.cll.2015.08.002
Hildenbrand P, Craven DE, Jones R, et al. Lyme neuroborreliosis: manifestations of a rapidly emerging zoonosis. Am J Neuroradiol. 2009;30(6):1079-1087. doi:10.3174/ajnr.A1579
Steere AC. Treatment of Lyme arthritis. J Rheumatol. 2019;46(8):871-873. doi:10.3899/jrheum.190320
Mead P, Petersen J, Hinckley A. Updated CDC recommendation for serologic diagnosis of Lyme disease. MMWR Morb Mortal Wkly Rep. 2019;68(32):703. doi:10.15585/mmwr.mm6832a4
B. burgdorferi IgG/IgM Test System. [Package insert]. ZEUS Scientific; 2020.
Branda JA, Body BA, Boyle J, et al. Advances in serodiagnostic testing for Lyme disease are at hand. Clin Infect Dis. 2017;66(7):1133-1139. doi:10.1093/cid/cix943
Kalish RA, McHugh G, Granquist J, et al. Persistence of immunoglobulin M or immunoglobulin G antibody responses to Borrelia burgdorferi 10–20 years after active Lyme disease. Clin Infect Dis. 2001;33(6):780-785. doi:10.1086/322669
Nocton JJ, Bloom BJ, Rutledge BJ, et al. Detection of Borrelia burgdorferi DNA by polymerase chain reaction in cerebrospinal fluid in Lyme neuroborreliosis. J Infect Dis. 1996;174(3):623-627. doi:10.1093/infdis/174.3.623
Blanc F, Jaulhac B, Fleury M, et al. Relevance of the antibody index to diagnose Lyme neuroborreliosis among seropositive patients. Neurology. 2007;69(10):953-958. doi:10.1212/01.wnl.0000269672.17807.e0
Aguero-Rosenfeld ME, Wang G, Schwartz I, et al. Diagnosis of Lyme borreliosis. Clin Microbiol Rev. 2005;18(3):484-509. doi:10.1128/CMR.18.3.484-509.2005
Sudhindra P, Wang G, Schriefer ME, et al. Insights into Borrelia miyamotoi infection from an untreated case demonstrating relapsing fever, monocytosis and a positive C6 Lyme serology. Diagn Microbiol Infect Dis. 2016;86(1):93-96. doi:10.1016/j.diagmicrobio.2016.06.015

Content reviewed 1/2026

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Test Code 6646

Lyme Disease Ab with Reflex to Blot (IgG, IgM)

Lyme disease is caused by a bacterium borrelia burgdorferi and is transmitted by ticks. A screening test with high sensitivity is used as the first step in the CDC recommended algorithm. Immunoblot testing qualitatively examines, with high specificity, antibodies in a patient's specimen. Immunoblot testing is appropriate for confirming a detected screening result.

Test Code 39218

Borrelia Species DNA, Real-Time PCR, with Reflexes, Synovial Fluid/CSF

This test is intended for the qualitative detection of Borrelia DNA in CSF or synovial fluid. Borrelia are spirochetes and are commonly classified into two categories: those that cause Lyme disease (Lyme borreliosis) and those that cause relapsing fever. This test detects species in both categories.

Borrelia are typically transmitted to humans via the bite of an infected tick, including hard-bodied ticks of the genera Amblyomma and Ixodes and soft

Test Code 90558

Tick ID with Reflex to Borrelia species DNA, Real-Time PCR, Tick

Identification of the Ixodes tick species will result in reflex to Real-Time PCR for detection of Borrelia species in the tick. The diagnosis of Borreliosis is most often made by clinical examination combined with evidence of a tick bite and/or exposure in endemic areas. Amplification of Borrelia genomic DNA from a tick can help support the diagnosis.

Test Code 15510

Borrelia species DNA, Qualitative Real-Time PCR, Tick

This test is intended for the qualitative detection of Borrelia DNA in ticks. Borrelia are spirochetes and are commonly classified into two categories: those that cause Lyme disease (Lyme borreliosis) and those that cause relapsing fever. This test detects species in both categories.

Borrelia are typically transmitted to humans via the bite of an infected tick, including hard-bodied ticks of the genera Amblyomma and Ixodes and soft-bodied ticks of the ge

Test Code 39733

Lyme Disease Antibody with Reflex to Immunoassay (IgG, IgM) (MTTT)

This test is for the qualitative detection of antibodies against Borrelia burgdorferi, the causative agent of Lyme disease, using the modified two-tier testing (MTTT) algorithm. Initial testing is performed using a Lyme total (IgG and IgM) antibody assay and if positive or equivocal, the sample is then tested using separate IgG and IgM immunoassays. This algorithm differs from the STTT algorithm in that the second-tier assays are chemiluminescent immunoassays, not immunoblots. MTTT may be

Test Code 16220

Tick-Borne Disease Antibodies Panel with Reflexes

This panel contains components for the detection of antibodies against Borrelia burgdorferi (Lyme disease) using the modified two-tier algorithm, Anaplasma phagocytophilum, Ehrlichia chaffeensis, and Babesia microti. Infection with these organisms can occur from the bite of a tick found in endemic regions, including the upper Northeast and Midwestern United States. Appropriate reflex testing of individual components is performed for initial screen results.

The

Test Code 15777

Borrelia Species DNA, Qualitative Real-Time PCR, Miscellaneous

This test is intended for the qualitative detection of Borrelia DNA in whole blood, CSF, or synovial fluid. Borrelia are spirochetes and are commonly classified into two categories: those that cause Lyme disease (Lyme borreliosis) and those that cause relapsing fever. This test detects species in both categories.

Borrelia are typically transmitted to humans via the bite of an infected tick, including hard-bodied ticks of the genera Amblyomma and Ixode

Test Code 93795

Borrelia miyamotoi DNA, Real-Time PCR, Miscellaneous

Persons infected with Borrelia miyamotoi most likely have fever, joint pains, fatigue, and headache, though unlike Lyme disease, rash is uncommon.
The diagnosis of Borrelia miyamotoi is most often made by history and clinical examination combined with exposure in endemic areas. Amplification of B. miyamotoi genomic DNA from blood, fluids or tissues confirms the diagnosis.

Test Code 34194

Lyme Disease Antibody Index for CNS Infection

The Lyme disease antibody index is used as an aid for diagnosing neuroborreliosis. The assay requires paired serum and CSF. A result set of lyme disease antibody index >1.2, control antibody index <1.0, and albumin ratio <0.0078 provides strong evidence of intrathecal synthesis of b. Burgdorferi antibodies and supports the diagnosis of neuroborreliosis.

Test Code 29477

Lyme Disease Antibody (IgG), Immunoblot

Lyme disease is caused by a tick vector carrying borrelia burgdorferi. Immunoblot testing qualitatively examines with high specificity antibodies in a patient's specimen. Immunoblot testing is appropriate for confirming a detected EIA or IFA test result.

Test Code 39684

Borrelia miyamotoi Antibodies (IgG, IgM), Immunoassay

Borrelia miyamotoi is a tick-borne bacterial organism that causes a nonspecific febrile illness that may be misdiagnosed as Lyme disease or other tick-borne infections. Positive antibody results suggest B. miyamotoi infection; however, other tick-borne organisms may induce cross-reactive antibodies. Negative IgG and IgM results do not exclude the possibility of B. miyamotoi infection.

Test Code 8593

Lyme Disease Antibodies (IgG, IgM), Immunoblot

Lyme disease is transmitted by a tick vector carrying Borrelia burgdorferi. Immunoblot testing qualitatively examines, with high specificity, antibodies in a patient's specimen. Immunoblot testing is appropriate for confirming a detected EIA or IFA test result.

Test Code 39209

Borrelia burgdorferi DNA, Qualitative Real-Time PCR, Miscellaneous

The diagnosis of Lyme disease is most often made by history and clinical examination combined with exposure in endemic areas. Amplification of Borrelia genomic DNA from blood, fluids or tissues can support the diagnosis. A negative result does not rule out Borrelia infection and appropriate serology testing may be clinically warranted.

Test Code 39219

Borrelia Species DNA, Real-Time PCR, with Reflexes, Blood

The diagnosis of Borreliosis is most often made by clinical examination combined with exposure in endemic areas. Amplification of Borrelia genomic DNA from blood can support the diagnosis. This test detects Borrelia species which are associated with either Lyme disease (Borrelia burgdorferi), or relapsing fever (Borrelia miyamotoi). A positive result for Borrelia species but negative result for Borrelia burgdorferi and Borrelia miyamotoi, may indi

Test Code 94322

Tick-borne Disease, Acute Molecular Panel

IG/Reference Manual

Test Guide List

This page is a complete list of Test Guides created by Quest Diagnostics.

Clinical Focus

Lyme Disease: Laboratory Support of Diagnosis and Management

This Clinical Focus provides information about laboratory tests related to Lyme disease.

Topic Brief

Tick-borne Disease: Laboratory Support of Diagnosis and Management

This Topic Brief provides information about the laboratory testing that supports the diagnosis of various types of tick-borne diseases.

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Reference ranges are provided as general guidance only. To interpret test results use the reference range in the laboratory report.

The tests listed by specialty and category are a select group of tests offered. For a complete list of Quest Diagnostics tests, please adjust the filter options chosen, or refer to our Directory of Services.

Lyme Disease: Laboratory Support of Diagnosis and Management

Lyme Disease: Laboratory Support of Diagnosis and Management

Clinical Focus

Clinical Focus

(15) Related Tests

(3) Related Guides