Persons infected with human immunodeficiency virus have an increased risk for development of high-grade, non-Hodgkin's lymphomas. Anaplastic large-cell Ki-1 lymphoma is a recently described lymphoid neoplasm characterized by cellular pleomorphism, a sinusoidal growth pattern, and Ki-1 epitope reactivity. This type of lymphoma is often mistaken for metastatic carcinoma, melanoma, or malignant histiocytosis. Although persons with acquired immunodeficiency syndrome frequently have non-Hodgkin's lymphoma at extranodal sites, the oral cavity and mandible, in particular, are unusual locations. We report two cases of anaplastic large-cell Ki-1 lymphoma that occurred in persons with the human immunodeficiency virus and with initial presentation as soft tissue masses of the posterior mandible. Immunocytochemical studies were positive for Ki-1 (CD30) in both cases. In situ hybridization for Epstein-Barr virus-deoxyribonucleic acid was positive with tumor cells in both cases. Flow cytometry on paraffin, formalin-fixed tissue revealed tetraploidy and high proliferative fractions that are characteristic of high-grade lymphomas. Intraoral presentation of rapidly enlarging, soft tissue masses may represent a high-grade non-Hodgkin's lymphoma in persons with the human immunodeficiency virus. Although rare, anaplastic large-cell Ki-1 lymphoma should be considered and requires immunocytochemical study to eliminate the possibility of other malignant conditions associated with the acquired immunodeficiency syndrome.