In the last few years, an increasing worldwide incidence in syphilis has been reported, mostly in the United States and Western Europe. Neurosyphilis is characterized by a wide differential diagnosis, which too often causes the disease to remain undetected for a long time. We report a case of a male patient with manic psychotic symptoms, in whom neurosyphilis was identified after elaborate diagnostic investigations. We give an overview of the disease process and correlations with psychiatric symptoms, diagnostics, screening and treatment.