Low-grade gastric lymphomas may be difficult to distinguish from benign inflammatory infiltrates on endoscopic biopsy specimens. Recent reports have suggested that so-called lymphoepithelial lesions (infiltration of lymphocytes into glandular epithelium) are characteristic of primary gastric lymphomas. We evaluated the presence and prominence of lymphoepithelial lesions and other histologic criteria in 25 low-grade gastric lymphomas (21 primary) and 58 benign inflammatory infiltrates to evaluate their utility in distinguishing benign from malignant gastric lymphoid infiltrates. The following features were associated only with lymphomas: (a) prominent (2-3 +) lymphoepithelial lesions (eight of 24 versus none of 58; p less than .0001); (b) Dutcher bodies (three of 25 versus none of 58, p = .05); and (c) moderate cytologic atypia (nine of 25 versus none of 58, p less than .0001). One or more of these features was seen in 18 of 25 gastric lymphomas (72%). Features more often associated with, but not limited to, lymphomas were dense (2-3 +) lymphoid infiltrates (25 of 25 versus five of 58, p less than .0001), rare or questionable lymphoepithelial lesions (11 of 24 versus 17 of 58, p = .01), muscularis mucosae invasion (20 of 20 versus 20 of 47, p less than .0001), ulceration (12 of 24 versus five of 58, p less than .0001), and mild cytologic atypia (eight of 25 versus six of 58, p less than .005). Germinal centers, crypt abscesses, and reactive epithelial atypia were seen with equal frequency in both types of infiltrate. Acute inflammation (2-3 +) was associated more often with inflammatory infiltrates (two of 25 versus 27 of 58, p less than .001). Our results suggest that dense lymphoid infiltrates with either prominent lymphoepithelial lesions, moderate cytologic atypia, or Dutcher bodies are highly suggestive and may be diagnostic of lymphoma. This constellation of findings is present in about 70% of endoscopic biopsy specimens of low-grade gastric lymphoma. In addition, the majority of cases of primary low-grade gastric lymphoma have morphologic, immunophenotypic, and clinical features that justify their inclusion in the category of low-grade lymphomas of mucosa-associated lymphoid tissue, whereas a minority are examples of lymphomatous polyposis of the gastrointestinal tract (centrocytic lymphoma).