A 61-year-old Japanese American woman was hospitalized with recalcitrant hypercalcemia of 3 months’ duration. Physical examination showed generalized cutaneous papules. The patient also had osteolytic bone lesions that caused fractures. On admission, the calcium level was 17.5 mg/dL (to convert to mmol/L, multiply by 0.25), and the parathyroid hormone level was suppressed. Peripheral blood smear showed a slight absolute lymphocytosis with occasional atypical lymphocytes. A skin biopsy specimen revealed a dense dermal infiltrate of atypical T lymphocytes with strong CD25 expression, characteristic of human T-cell lymphotropic virus type 1 (HTLV-1)–associated adult T-cell leukemia/lymphoma (ATCLL). Serologic testing for HTLV-1 was subsequently shown to be positive. The HTLV-1 is endemic in Japan, the Caribbean, Central Africa, and the southeastern United States. Infection is transmitted by sexual contact, blood transfusion, or mother-to-child vertical transmission. The HTLV-1 genome is clonally integrated into the DNA of the lymphoma cells. The clinical differential diagnosis of the skin findings in this patient included generalized histiocytic disorders, leukemia cutis, and other types of lymphoma. The diagnosis is established through identification of the leukemia/lymphoma cells within the peripheral blood, skin, or other affected organs. The strong expression of CD25 by the lymphoma cells is a characteristic immunophenotypic finding. With conventional systemic chemotherapy regimens, the prognosis for patients with ATCLL is poor. Recent studies have examined other potentially more promising treatments, such as allogeneic stem cell transplant, alemtuzumab, denileukin diftitox, or antiviral agents. Although rare in the United States, ATCLL should be considered in patients from endemic areas who present with cutaneous lymphoid infiltrates, hypercalcemia, and osteolytic bone lesions.