In sera from 476 diabetic outpatients, positive reaction in the Fluorescent Treponemal Antibody-Absorption (FTA-Abs) test, a commonly used serological test for syphilis, was found in 36 of the patients. None of 100 healthy control subjects were positive in the FTA-Abs test. Additional treponemal and nontreponemal tests confirmed the diagnosis of syphilis in only three of the diabetic patients. In 10 of the 36 patients, the positive FTA-Abs reactivity appeared to be due to cross-reactivity between the treponemal antigen and Borrelia burgdorferi, which causes Lyme borreliosis. In the remaining 23 patients (5%), no other explanation for a false-positive FTA-Abs reactivity was found besides diabetes. Diabetic patients with false-positive FTA-Abs reactivity had similar degree of long-term metabolic control and prevalence of islet cell antibodies (ICA) as well as late diabetic complications as FTA-Abs negative diabetic patients, matched regarding to sex, age, type, and duration of diabetes. In conclusion, false-positive FTA-Abs reactivity is not rare in diabetic patients. The reason for this phenomenon is unknown, but could be a sign of autoimmunity of its own. Hence, in diabetic patients with FTA-Abs test indicating syphilis, the diagnosis must be verified with a combination of other tests.