Diagnosis begins with a complete medical history (including sexual history) and a physical examination. Based on those results, physicians use several types of tests to diagnose syphilis. In many cases, physicians must repeat diagnostic tests because the disease is less detectable in its early stages. Some diagnostic methods are more effective than others, depending on the stage of the disease. Physicians frequently use some or all of these methods to diagnose syphilis.

• Visualization. A physician can usually identify the chancres (sores) of primary syphilis on sight.
  
  
• Dark field imaging. A specialized microscope is used to identify the syphilis bacteria. A sample from a chancre or lesion is used or fluid is taken from a lymph node. This test usually involves swabbing a chancre, infected skin or mucous membrane, or using a needle to obtain fluid from the chancre or an infected lymph node. The liquid or sample is placed on a slide and viewed through a special dark-field microscope. This method is effective for detecting primary and secondary syphilis.
  
  
• Screening tests. Physicians may use a test that screens for a certain antibody not related to syphilis (nontreponemal tests). These include the venereal disease research laboratory (VDRL) or rapid plasma reagin (RPR) tests. Both tests may use blood or spinal fluid, but blood is much more common. Spinal fluid testing is usually only performed in cases of suspected tertiary syphilis. To obtain spinal fluid, the physician performs a spinal tap by inserting a needle into the lower back and collecting the cerebrospinal fluid. These tests are useful for detecting tertiary syphilis, but not primary or secondary syphilis. They may also produce false positives. Many other conditions, including pneumonia, blood transfusions or pregnancy, may produce positive reactions on the VDRL and RPR tests.
  
  
• Treponemal antibody tests. If the screening tests have positive reactions, a physician may recommend a blood test to detect the presence of antibodies to the Treponema pallidum bacteria. These blood tests include:
  
  
• Fluorescent treponemal antibody absorption (FTA–ABS). May also be used with spinal fluid.
  
  
• Microhemagglutination assay for antibodies to Treponema pallidum (MHA–TP). This test is rarely used.
  
  
• Treponema pallidum particle agglutination (TPPA).

These tests are accurate except in the first few weeks after infection. In addition, a patient treated for a previous case of syphilis will continue to test positive because they have antibodies to the disease but can still be re-infected. In these cases, re-infection is determined by a rise in the level of certain antibodies.