The authors report an unusual large cell lymphoma of the rectum composed of large granular lymphocytes (LGL) with histologic characteristics of an angiocentric growth pattern. Immunophenotyping showed that most of the tumor cells were CD3-, CD4-, CD8+, CD16+, CD56+, and CD57-. Fine structural analysis of the tumor cells found substantial numbers of electron-dense granules. Genotypic investigation showed a germline configuration of the T-cell receptor beta and gamma chain genes and the immunoglobulin heavy chain gene. The clinical course was aggressive, with rapid dissemination to the lungs, liver, and subcutis. The lesion was resistant to chemotherapy. There was, however, no evidence for peripheral blood or bone marrow involvement. This case report demonstrates the need for continued inquiry into the possible association of LGL with angiocentric lymphoproliferative lesions and gut-associated T-lymphocyte lesions.