A 31-year-old man with well-controlled infection with the human immunodeficiency virus presented to the clinic with a 1-week history of a painless genital rash and a 2-day history of fever and sore throat. Three weeks earlier, he had had condomless intercourse with a new male partner. On physical examination, a macular rash and painful lymphadenopathy were observed in the right inguinal area (Panel A), and two ulcerated lesions and several umbilicated pustules were observed on the penis (Panel B). Tests for syphilis, chlamydia, and gonorrhea were negative. Antimicrobial therapy for possible lymphogranuloma venereum and chancroid was initiated. Five days after the initial presentation, the patient returned with vesiculopustular lesions on the face and hands. Polymerase-chain-reaction assays of swabs obtained from lesions on the genitals and the hands were positive for monkeypox. In classic cases of monkeypox, patients have a febrile prodrome followed by a rash that may appear on any part of the body, with lesions that evolve simultaneously. In the current global outbreak of monkeypox, painless anogenital lesions — often without a prodrome — are being observed in persons who have had close contact with an infected person or persons, including men who have sex with men. Within 2 weeks after his initial presentation, the patient’s lesions had abated without specific intervention. Additional examples of monkeypox genital lesions that were observed in other patients are shown in Panels C and D