A 62-year-old man presented to the emergency department with a 2-week history of generalized weakness and a diffuse rash. On examination he had a temperature of 38.1°C (100.6°F). Physical examination showed a maculopapular, hyperpigmented, and scaly eruption on his palms (Panel A), soles (Panel B), and trunk (Panel C). There were also hypopigmented plaques on the genitals. He had a history of unprotected intercourse with multiple partners but had not noted the presence of chancres or genital ulcerations. A rapid plasma reagin test was conducted and revealed an elevated titer of 1:128. A fluorescent treponemal antibody absorption test was reactive. Testing for human immunodeficiency virus was negative. A diagnosis of secondary syphilis was made. Primary infection may be asymptomatic; an initial, painless chancre may go unnoticed. The patient was treated with intramuscular penicillin G benzathine and at follow-up 3 months later had complete resolution of the rash and a reduced rapid plasma reagin titer of 1:32.