In the last 20 years, there has been a decrease in the prevalence of syphilis and a change in the structure of the incidence. The number of latent and late forms, including vascular syphilis and neurosyphilis, has increased. The issue of timely diagnosis of syphilis remains relevant. Despite the broad options of laboratory tests, establishing the correct diagnosis is often challenging for doctors of related specialties. Sometimes, there is a poor-quality medical history and incorrect interpretation of clinical manifestations and laboratory tests. The paper presents four clinical cases when related specialists could not recognize syphilis promptly, and specific therapy was started late. To promote preventive measures, it is necessary to regularly improve the skills of doctors of various specialties in the clinical presentation interpretation and early diagnosis of syphilis. The development of diagnostic criteria, new informative methods of laboratory diagnostics, their timely use, and correct interpretation of the results will reduce the number of incorrect and untimely diagnoses and choose the right therapeutic strategy. Only in this way is it possible to start specific treatment promptly, which is paramount for the patient and other subjects.