A 44-year-old man with a history of human immunodeficiency virus infection and intermittent adherence to antiretroviral therapy presented to the infectious disease clinic with a 1-month history of fevers and pruritic skin lesions. His temperature was 38.3°C. Physical examination was notable for blackish-brown lamellated plaques on the limbs and scalp. Laboratory studies were notable for a CD4 cell count of 86 per cubic millimeter (reference range, 414 to 1123), a viral load of 35,900 copies per milliliter (reference value, <20), and a rapid plasma reagin titer of 1:32. A Treponema pallidum particle agglutination assay was positive. A skin-biopsy specimen of the left forearm showed diffuse dermal lymphocytes and histiocytes admixed with a plasma-cell infiltrate. A diagnosis of malignant syphilis was made. Malignant syphilis is an uncommon form of secondary syphilis that primarily affects immunocompromised persons. The skin manifestations are varied, ranging from ulceronodular lesions to oyster shell–like crusts, the latter of which were seen in this patient. The patient declined a lumbar puncture to evaluate for . He also declined penicillin desensitization, which had been offered because of his history of anaphylaxis to penicillin. After a 2-week course of intravenous ceftriaxone, the skin lesions and fevers abated. At a 3-month follow-up visit, the rapid plasma reagin titer had decreased to 1:2.