Syphilis is still a serious disease with diagnostic difficulties. In the present clinical case a patient had a routine serology screen for syphilis and HIV at a venerology clinic. He had previously presented with anogenital tumors, but the diagnosis was uncertain. A polymerase chain reaction (PCR) analysis was performed in addition to serology, and the diagnosis of syphilis in the secondary stage was confirmed. This case demonstrates how PCR technology can assist in the diagnosis of syphilis at early stages and underlines the importance of syphilis screening in homosexual men presenting with anogenital complaints.