Syphilis is a re-emerging disease, and suspicion of syphilis infection should be considered in all cases with atypical skin manifestations, mainly when there is a history of unprotected sexual intercourse. Here, we describe a case of secondary syphilis in a woman aged 42 years, who presented with an atypical, painful and itchy skin rash with vegetative cerebriform lesions, which resolved after the administration of penicillin. Multiplex PCR targeting