A distinctive type of low-grade extranodal lymphoma recapitulates the cytomorphologic features of mucosa-associated lymphoid tissue (MALT). Typically, these MALT lymphomas arise from sites normally devoid of lymphoid tissue, but are preceded by chronic inflammatory, usually autoimmune, disorders that result in the accumulation of lymphoid tissue. The stomach is the most common site of MALT lymphoma, which arises from lymphoid tissue acquired as the result of Helicobacter pylori infection. The indolent clinical behavior of gastric MALT lymphoma coupled with certain histologic features suggests that its growth is subject to immunologic stimuli, and the role of H pylori in this respect has been examined in detail. In vitro experiments have shown that the growth of lymphoma cells is stimulated by contact with T cells, which, in turn, show strain specific responses to heat-killed H pylori. Clinically, approximately 70% of cases of stage IE gastric MALT lymphoma regress following eradication of H pylori with antibiotics. Large, deeply invasive tumors and those that have undergone high-grade transformation typically do not respond to antibiotic therapy. Other common sites of MALT lymphoma include the salivary glands, lung, and ocular adnexa. The clinicopathologic features of these lymphomas are remarkably similar to gastric MALT lymphoma, which suggests that they, too, may be antigen-driven.