Three cases of extranodal marginal zone B-cell lymphoma (low grade B-cell lymphoma of mucosa-associated lymphoid tissue [MALT] type) in which the neoplastic B cells expressed the CD5 antigen are reported. The patients included 2 men and 1 woman, aged 44, 62, and 77 years. In all three cases, the histologic features were typical of marginal zone/MALT lymphoma, with reactive follicles, marginal zone (centrocyte-like) cells, and plasma cells. Pseudofollicles, prolymphocytes, and paraimmunoblasts were absent. In all cases, lymphoma from one or more sites expressed monotypic immunoglobulin (2 IgM kappa, 1 IgM lambda), pan B cell antigens and CD5. Two of 3 cases expressed CD43; one case expressed CD23. No case showed overexpression of the bcl-1 protein, cyclin D1. Interphase cytogenetic analysis revealed trisomy 3 in one of two cases examined. The two male patients presented with lymphoma in the ocular adnexa. One of them had marrow involvement, cervical lymphadenopathy and peripheral blood involvement at presentation; 24 months later, he developed a relapse in subcutaneous tissue. The second patient had marrow involvement 3 years later, at the time of recurrence of his orbital disease. The third patient presented with lymphoma at the base of the tongue. She subsequently developed lymphoma involving the left upper eyelid and right lacrimal sac and duct, the marrow, and the nasopharynx between 63 and 95 months after initial presentation. All of these patients presented with disease involving sites in the head and neck and all had multiple relapses or recurrences with bone marrow involvement at the time of presentation (1 case) or at relapse (2 cases). The presence of CD5 may be a marker for cases of MALT lymphoma with a tendency for persistent or recurrent disease, for dissemination to the marrow and other extranodal sites, and for leukemic involvement of the peripheral blood.