Rare cases of low-grade lymphomas have been described in patients with human immunodeficiency virus (HIV) infection. However, this is the first reported case of mantle-cell lymphoma, a type of low-grade lymphoma, in a patient who also had HIV infection. Salient clinical features included lymphocytosis, lymphadenopathy, splenomegaly, and involvement of the bone marrow and meninges. The disease proved to be unusually aggressive and response to chemotherapy was insignificant. The patient survived only 4 months.