Helicobacter pylori in humans is associated with active, chronic gastritis, peptic ulcer disease, and most recently has been linked epidemiologically to gastric adenocarcinoma. A related organism, Helicobacter mustelae, naturally infects ferrets and also causes a persistent gastritis, a precancerous lesion, and focal glandular atrophy of the proximal antrum. In this report, we document the clinical presentation and histopathologic confirmation of H. mustelae-associated gastric adenocarcinoma in two middle-aged male ferrets. The ferret appears to be well suited to study the pathogenesis of naturally occurring Helicobacter sp.-induced gastric adenocarcinoma.