In my clinic, I often encounter patients who come in for a positive syphilis test after a physical exam, blood donation or pre-operative exam. They are often confused about how they got syphilis, whether it was due to their husbands cheating on them, whether they got infected during blood donation or during childbirth, and so on. In fact, non-syphilis spirochete antibody tests (e.g. RPR, TRUST, VDRL) often give false positive results, which is clinically referred to as a “biological false positive”. False positives for syphilis are often seen in many non-syphilis related conditions (e.g. HIV infection, autoimmune diseases, etc.) or in special circumstances (e.g. pregnancy, injecting drug use, elderly, vaccinations, etc.). Therefore, the easiest way to rule out a false positive syphilis is to have a confirmatory syphilis test (e.g. TPPA, TPHA, FTA-ABS, etc.), and if the result is negative, syphilis infection can be ruled out.