Mantle cell lymphoma is a distinct subtype and accounts for approximately 5 to 10% of non-Hodgkin lymphomas. The malignant cells express pan B-cell markers, including CD19, CD20 and CD22, and the T-cell marker CD5, whereas CD10 and CD23 expression are usually absent. By cytogenetic analysis, the t(11;14)(q13;q32) translocation is commonly observed, resulting in overexpression of cyclin D1. This entity often combines some unfavorable clinical features of the indolent and aggressive lymphoma subtypes, as it is generally incurable and relatively aggressive. It is most commonly observed in men 50 to 70 years of age and is characterized by disseminated disease, usually involving lymph nodes, bone marrow, and spleen. Frequently, there is extranodal involvement including the gastrointestinal tract. These tumors are incurable with the currently available therapeutic options, with usual time to progression after chemotherapy of approximately 1 year. Newer chemotherapy regimens (including stem cell transplantation) and monoclonal antibody-based therapies have shown limited evidence of additional benefit. Overall, the prognosis for patients with mantle cell lymphoma remains poor, and novel strategies are needed.