There is growing evidence to support new modes of transmission for human monkeypox infection. As these methods are being explored, this report delineates the day-to-day clinical sequelae following the initial exposure in an HIV-positive man who had sexual intercourse with another man days preceding his infection. We describe atypical cutaneous manifestations involving widespread erythematous pustules with preceding anogenital ulcerations and concomitant bilateral inguinal lymphadenopathy. Clinicopathologic correlation is used to assist in the workup and establishing the diagnosis. Our case supports others reported in the literature that suggest sexual contact as a means of transmission. More research is needed that investigates the presence of infection in both men and women, including those who could act as carriers, to elucidate other pathways in this evolving yet evasive viral disease.