A 37-year-old Caucasian male, HIV-infected (CDC A2) in 2012 and on antiretroviral therapy, presented for a follow-up visit. On physical examination, a barely discernible light-colored macular rash was observed on the trunk, not involving the palms and soles. However, clear maculo-papular lesions were present over the proximal volar aspect of both forearms. Furthermore, well-demarked purplish, opaque, rough, vertically ridged plaque-like lesions were observed over the proximal portions of fingernails. The patient reported that cutaneous and nail lesions had appeared about 2 months prior and that he had engaged in unprotected sex 5 months before. Serologic tests for syphilis resulted reactive. Intramuscular injection of benzathine penicillin G, 2.4 million units, was administered once a week for 3 weeks. One month after therapy, the rash was no longer present, and at 5 months, nail abnormalities had disappeared. The clinical findings, the serologic results, and the disappearance of skin and nail lesions after the administration of penicillin strongly suggest that this HIV-infected patient had secondary or early late syphilis with skin and nail-plate involvement. We are experiencing a resurgence of syphilis as well as an increase in unusual and/or forgotten clinical manifestations. Syphilis remains a diagnostically challenging disease.