The clinical presentation and endoscopic appearance of gastric lymphoma are similar to those of adenocarcinoma. Most patients have abdominal pain, weight loss, or bleeding. Patients with diffuse large B-cell lymphoma are more likely to have systemic symptoms and advanced tumor stage. At endoscopy, lymphoma may appear as an ulcer, mass, or diffusely infiltrating lesion. It tends to have horizontal infiltration as opposed to the vertical extension seen in adenocarcinoma. The diagnosis is established with endoscopic biopsy; FNA is not adequate. Since the disease can be multifocal, biopsies of both suspicious and normal-appearing areas are recommended. Biopsy specimens should be tested for H pylori and, if positive, for t(11;18) via PCR or FISH. EUS is the most sensitive test for determining the level of invasion and presence of perigastric lymphadenopathy and should be performed for accurate staging, if available. All patients should undergo staging with CT scanning of chest, abdomen, and pelvis. For gastric MALT lymphomas, the Lugano staging system is most frequently used. Stage I is confined to the gastrointestinal tract, stage II involves local or regional lymph nodes, stage IIE has invasion of adjacent organs or tissues, and stage IV has distant metastases. There is no stage III. For patients with diffuse large B-cell lymphomas involving the stomach, combination PET-CT imaging, bone marrow biopsy with aspirate, tumor lysis laboratory tests, and hepatitis B and HIV serologies also may be required for staging and treatment planning (see Chapter 13).