A 33-year-old man presented to the emergency department with fatigue and with lesions in the oral cavity and on the skin. Physical examination revealed multiple, firm, nontender, violaceous plaques of the palate and gums. He had similar lesions on his face, chest wall, and legs. Laboratory studies revealed leukopenia (white-cell count, 2900 per cubic millimeter; normal range, 4000 to 11,000) and a CD4 count of 76 cells per cubic millimeter (normal range, 430 to 1276). A diagnosis of human immunodeficiency virus infection was made. Biopsies of the skin and oral lesions revealed spindle-cell neoplasm, which was positive for CD34 and human herpesvirus 8 on immunohistochemical testing — findings that are consistent with Kaposi’s sarcoma. Antiretroviral therapy (ART) and chemotherapy were both initiated. Kaposi’s sarcoma, a cancer that indicates the presence of an immunodeficient state, is caused by human herpesvirus 8. Cutaneous lesions may occur alone or with visceral lesions of the oral cavity, gastrointestinal tract, and respiratory system. The presence of extensive oral Kaposi’s sarcoma, as seen in this patient, is associated with a poor prognosis. After several months of treatment, the tumors in this patient diminished in size. Several months after the completion of chemotherapy, the patient is continuing to take ART, with an increased CD4 count and no progression of the oral and skin lesions.