A 72-year-old man presented after several months of dyspepsia and 1 day of hematemesis. He was not taking NSAIDs. Drs Lucia C. Fry and Klaus E. Mönkemüller of Birmingham, Ala, report that the patient was pale; heart rate was 100 beats per minute and blood pressure, 120/70 mm Hg, with no orthostasis. Multiple, oval-shaped ulcers in the fundus, body, and antrum of the stomach and thickened gastric folds were noted on an endoscopic examination of the upper GI tract. Histopathologic examination of multiple biopsy specimens revealed a high-grade mucosa-associated lymphoid tissue (MALT) lymphoma. Although lymphomas comprise fewer than 5% of all gastric malignancies, they are the second most common stomach neoplasms; adenocarcinomas occur more frequently. Recent evidence suggests that the incidence of lymphoma may be increasing, whereas the occurrence of adenocarcinoma is decreasing.1,2 The GI tract, particularly the stomach and small bowel, is the most common extranodal site of lymphomas; as many as 46% occur in the stomach.1 Most frequently, these lesions are non-Hodgkin lymphomas that are derived from MALT. There is strong evidence that Helicobacter pylori plays a crucial role in the genesis of primary gastric lymphoma. Reactive follicles and glandular infiltration often surround MALT lymphomas, and epidemiologic studies show that the prevalence of H pylori infection in affected patients is about 90%.3,4 Patients with lymphoma and those with adenocarcinoma present with similar symptoms, including weight loss, anemia, hematemesis, abdominal pain, and nausea or vomiting. On a barium enema examination, thickened gastric folds, multiple masses, and areas of ulceration suggest lymphoma. Lymphomas may also appear as polypoid, ulcerating, or infiltrative lesions. An endoscopic biopsy may provide the diagnosis when the lesion is polypoid or ulcerative; a full-thickness (ie, transmural) tissue biopsy is needed for infiltrative lesions. Patients with low-grade lymphomas usually can be treated with anti–H pylori therapy, including proton pump inhibitors and clarithromycin(Drug information on clarithromycin) and amoxicillin(Drug information on amoxicillin) or metronidazole(Drug information on metronidazole); whereas those with high-grade tumors or infiltrative lymphomas require chemotherapy and/or radiation therapy. Surgery may be helpful in some cases. This patient responded well to chemotherapy with cyclophosphamide(Drug information on cyclophosphamide), hydroxydaunomycin, vincristine, and prednisone(Drug information on prednisone) (CHOP). Because he tested positive for H pylori, antibiotics were given as well.