Background: Lymphomatous neoplasia of the stomach is initially seen either as primary gastric B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) or as nodal non-Hodgkin ́s lymphoma (NHL) secondarily involving the GI tract. One hundred seventy-six patients with primary gastric NHL (low grade, n = 65; high grade, n = 111) and 29 with secondary gastric NHL (low grade, n = 19; high grade, n = 10) were studied to evaluate whether differences in pathogenesis are associated with distinct clinical and endoscopic features. Methods: Clinical features, tumor size, localization, and growth pattern were analyzed by means of esophagogastroduodenoscopy; grading was determined with histologic examination. Results: The analysis of various clinical symptoms and endoscopic findings revealed a relationship between the occurrence of abdominal pain, vomiting, and unifocal growth pattern with an affiliation to the group with primary gastric NHL (p < 0.001), whereas tumor localization in the gastric fundus was predominantly found in secondary gastric NHL (p < 0.001). An equation has been generated that may help to predict affiliation to primary or secondary gastric NHL with an accuracy of 96%. Conclusions: Our results indicate that careful pretreatment analysis of clinical and endoscopic findings may be helpful in the diagnosis of primary or secondary gastric involvement by NHL, although reliable discrimination still requires histologic verification. (Gastrointest Endosc 1999;49:307-15.)