Diagnosis of Lyme disease begins with a medical history, including questions about exposure to deer ticks, and a physical examination, including inspection of the skin for the red rash known as erythema migrans (EM).  

However, this disease is often difficult to diagnose. Its symptoms can be confused with indicators of other conditions, such as fibromyalgia or chronic fatigue syndrome. Also, some people in an endemic (infected) area may have the disease without the rash or other signs and symptoms. Usually the patient has a lot of testing before Lyme disease is diagnosed.

Consequently, several tests may be used in diagnosis, such as:

• Enzyme-linked immunosorbent assay (ELISA) test. Antibodies that fight Lyme disease bacteria are measured using the ELISA blood test. These antibodies take time to develop. As a result, many people with early localized Lyme disease have a negative ELISA test result. Furthermore, some individuals who do not have Lyme disease falsely test positive because of similarities between Borrelia burgdorferi (the bacteria that cause Lyme disease) and other organisms normally found in the body.
  
  
• Western blot test. This blood test is used to either prove or disprove ELISA test results when they are either positive or inconclusive. Western blot test is also useful in determining when an ELISA test is falsely positive.
  
  
• Spinal tap (lumbar puncture). A needle inserted through the lower back withdraws a sample of cerebrospinal fluid (the fluid surrounding the brain and spinal cord) for laboratory analysis. The procedure may be used if meningitis or encephalitis is suspected.   
  
  
• Imaging. CAT scan (computed axial tomography) or MRI (magnetic resonance imaging) of the brain may be performed to rule out the presence of other conditions with symptoms similar to Lyme disease. An electrocardiogram (ECG or EKG) may be performed if possible heart complications are present.  

• Skin biopsy. Rarely, a sample of skin tissue may be taken and analyzed to identify the bacteria.

The presence of erythema migrans is important in diagnosis of Lyme disease. Unlike many other types of infections, blood tests for Lyme disease are sometimes falsely positive (inaccurately indicating the disease where it is not present) when there are only nonspecific symptoms. In an attempt to avoid unnecessary treatment, blood tests are rarely performed when EM is not present.