Gastric lymphoma resembling gastric mucosa-associated lymphoid tissue (MALT) lymphoma linked with Helicobacter pylori infection in humans was observed in ferrets infected with H. mustelae. Four ferrets with ante- or postmortem evidence of primary gastric lymphoma were described. Lymphoma was diagnosed in the wall of the lesser curvature of the pyloric antrum, corresponding to the predominant focus of H. mustelae induced gastritis in ferrets. Two ferrets had low-grade small-cell lymphoma and two ferrets had high-grade large-cell lymphoma. Gastric lymphomas demonstrated characteristic lymphoepithelial lesions, and the lymphoid cells were IgG+ in all ferrets. Lymphoma was confirmed by light chain restriction, which contrasted with the 1.2:1 kappa lambda ratio observed in H. mustelae-associated chronic gastritis. H. mustelae infection in ferrets has been used as a model for gastritis, ulcerogenesis, and carcinogenesis. The ferret may provide an attractive model to study pathogenesis and treatment of gastric MALT lymphoma in humans.