Lyme diagnosis and testing can be very confusing, which has contributed to false positive diagnoses and unnecessary treatment.
According to the CDC:
- Patients who have had Lyme disease for longer than 4-6 weeks, especially those with later stages of illness involving the brain or the joints, will almost always test positive.
- A patient who has been ill for months or years and has a negative test almost certainly does not have Lyme disease as the cause of their symptoms.
- Serologic testing is generally not useful or recommended for patients with single EM rashes. For this manifestation, a clinical diagnosis (alone) is recommended.
A 2016 systematic review  that included 8 studies of test performance in “Late Lyme” showed Lyme antibody testing to be 99.4% sensitive and 99.3% specific**.
In other words, out of 100 people with Late Lyme disease, 99-100 of them will test positive. Out of 100 people who may believe they have Late Lyme disease but do not, 99-100 of them will test negative.
Avoid unnecessary and unscientific testing
Don’t test for Lyme disease as a cause of musculoskeletal symptoms without an exposure history and appropriate exam findings. 
The CDC has expressed similar sentiments  to the ACR and has also warned against unvalidated testing [5, 9]. Quackwatch  and Science-Based Medicine  both provide accessible explanations about the differences between validated and unvalidated tests.
See also the following LymeScience pages:
- How chronic Lyme recruits followers
- Lyme misdiagnosis illustrated
- Red flags of chronic Lyme quackery
- CDC scientist: Why bands 31 and 34 aren’t used to test for Lyme disease
- CD57 testing and chronic Lyme: Meaningless and a waste of money
Other misconceptions about Lyme disease diagnosis and testing are discussed below.
Table excerpted and reformatted* from the longer 2013 paper (ref 2 below, which is worth reading):
There is substantial evidence supporting the accuracy of FDA-cleared tests once antibodies build up in the body (4-6 weeks post-infection).
The CDC concurs:
You may have heard that the blood test for Lyme disease is correctly positive only 65% of the time or less. This is misleading information. As with serologic tests for other infectious diseases, the accuracy of the test depends upon the stage of disease. During the first few weeks of infection, such as when a patient has an erythema migrans rash, the test is expected to be negative.
Several weeks after infection, currently available ELISA, EIA and IFA tests and two-tier testing have very good sensitivity.
It is possible for someone who was infected with Lyme disease to test negative because:
- Some people who receive antibiotics (e.g., doxycycline) early in disease (within the first few weeks after tick bite) may not develop antibodies or may only develop them at levels too low to be detected by the test.
- Antibodies against Lyme disease bacteria usually take a few weeks to develop, so tests performed before this time may be negative even if the person is infected. In this case, if the person is retested a few weeks later, they should have a positive test if they have Lyme disease. It is not until 4 to 6 weeks have passed that the test is likely to be positive. This does not mean that the test is bad, only that it needs to be used correctly. 
* LymeScience reformatted the table and added punctuation, emphasis, a note, and changed the word “evidence” to “science”. Excerpted for educational and commentary purposes.
** 99.4% sensitive (95% confidence interval: 95.7–99.9) and 99.3% (95% confidence interval: 98.5-99.7%) specific.
1. Choosing Wisely: American College of Rheumatology
2. Halperin JJ, Baker P, Wormser GP. Common misconceptions about Lyme disease. Am J Med. 2013 Mar;126(3):264.e1-7.
3. CDC: Three Sudden Cardiac Deaths Associated with Lyme Carditis — United States, November 2012–July 2013
4. CDC: Lyme disease: Diagnosis and Testing
5. CDC: Lyme disease: Laboratory tests that are not recommended
6. CDC scientist Barbara J.B. Johnson, PhD: Book chapter of “Lyme disease: An Evidence-Based Approach”: Laboratory Diagnostic Testing for Borrelia burgdorferi Infection
7. CDC: “I have heard that the diagnostic tests that CDC recommends are not very accurate. Can I be treated based on my symptoms or do I need to use a different test?” Lyme FAQ.
8. Waddell LA, et al. The Accuracy of Diagnostic Tests for Lyme Disease in Humans, A Systematic Review and Meta-Analysis of North American Research. PLoS ONE. 2016;11(12):e0168613.
9. CDC: Notice to Readers: Caution Regarding Testing for Lyme Disease
10. Quackwatch: Some Notes on Nonstandard Lyme Disease Tests
11. Science-Based Medicine: Lemons and Lyme: Bogus tests and dangerous treatments of the Lyme-literati
12. American Lyme Disease Foundation: Limitations of Antibody-Based Diagnostic Tests for Lyme Disease
13. Botman E, et al. Diagnostic behaviour of general practitioners when suspecting Lyme disease: a database study from 2010-2015. BMC Fam Pract. 2018;19(1):43.
14. Article about “ELISpot” Lyme tests: New test has no added value in Lyme disease of the central nervous system
15. Duerden BI. Unorthodox and unvalidated laboratory tests in the diagnosis of Lyme borreliosis and in relation to medically unexplained symptoms. Department of Health, London, UK, 2006.
16. CDC Q and A: Epidemiology and Clinical Features of Lyme Disease
17. Choosing Wisely: Lyme Disease
18. Canadian scientists: Lyme disease: How reliable are serologic results?