Syphilis has sometimes been called "the great imitator" because its early symptoms are similar to those of many other diseases. Sexually active people should consult a doctor about any suspicious rash or sore in the genital area. Those who have been treated for another STD, such as gonorrhea, should be tested to be sure they have not also acquired syphilis.

There are three ways to diagnose syphilis:
1. a doctor's recognition of its signs and symptoms
2. microscopic identification of syphilis bacteria
3. blood tests

The doctor usually uses these approaches together to detect syphilis and decide upon the stage of infection.

To diagnose syphilis by identifying the bacteria, the doctor takes a scraping from the surface of the ulcer or chancre, and examines it under a special "darkfield" microscope to detect the organism itself. Blood tests also provide evidence of infection, although they may give false- negative results (not show signs of infection despite its presence) for up to three months after infection. False-positive tests also can occur; therefore, two blood tests are usually used. Interpretation of blood tests for syphilis can be difficult, and repeated tests are sometimes necessary to confirm the diagnosis.

The blood-screening tests most often used to detect evidence of syphilis are the VDRL (Venereal Disease Research Laboratory) test and the RPR (rapid plasma reagin) test. The false-positive results (showing signs of infection when it is not present) occur in people with autoimmune disorders, certain viral infections, and other conditions.

Therefore, a doctor will administer a confirmatory blood test when the initial test is positive. These tests include the fluorescent treponemal antibody-absorption (FTA-ABS) test that can accurately detect 70 to 90 percent of cases. Another specific test is the T. pallidum hemagglutination assay (TPHA). These tests detect syphilis antibodies (proteins made by a person's immune system to fight infection). They are not useful for diagnosing a new case of syphilis in patients who have had the disease previously because once antibodies are formed, they remain in the body for many years. These antibodies, however, do not protect against a new syphilis infection. In some patients with syphilis (especially in the latent or late stages), a lumbar puncture (spinal tap) must be done to check for infection of the nervous system.