The epidemiologic situation of syphilitic infection warrants attention to diagnostic methods. Nontreponemal tests (rapid plasma regain, Venereal Disease Research Laboratory) are less reliable, as there are certain situations when false-positive reactions for syphilis antibodies may appear. Variable examinations were performed and proved that it was necessary to assess the titer of antibodies, as well as confirmation of the diagnosis by treponemal tests (fluorescent treponemal antibody, treponema pallidum hemagglutination assay, enzyme immunoassay, Western blot), were obligatory. In recent decades, new methods were elaborated (e.g., BioPlex total screen, tests with β2-GPI-dependent anticardiolipin antibody, the ARCHITECT syphilis treponema pallidum chemiluminescent immunoassay, the Elecsys immunoassay (Roche Diagnostics)). We present the review of publications on syphilis serologic diagnostics and present our own research. We did not find any mention of a false-positive test in atopic dermatitis and present a case of false-positive reactions for syphilis in such patients.