A previously healthy 25-year-old man presented with a 2-week history of multiple nonpruritic, well-circumscribed, scale-covered, erythematous plaques on his palms and soles (Panels A and B, respectively). He was otherwise asymptomatic, and a physical examination was unremarkable. He specifically reported not having a history of genital ulceration but did report having unprotected sexual intercourse with multiple female partners. A Venereal Disease Research Laboratory test was positive at a titer of 1:64, and a microhemagglutination assay for antibodies against Treponema pallidum (MHA-TP) was reactive, confirming a diagnosis of secondary syphilis. Tests for chlamydia, gonorrhea, and human immunodeficiency virus were all negative. The patient was treated with a single intramuscular dose of 2.4 million units of penicillin G benzathine, resulting in the resolution of his rash.