Introduction: Gastric MALT (mucosa-associated lymphoid tissue) lymphoma is a type of non-Hodgkin's lymphoma with concomitant H. pylori infection. Approximately 5-10% of patients are not. Recent studies on H. pylori-negative gastric MALT lymphomas have suggested that H. pylori eradication therapy is effective in a proportion of patients with this disease and could even be considered a first-line treatment. Here, we present this uncommon and unique case. Case Description/Methods: A 58-year-old man, with PMH of prostate cancer and DVT not on anticoagulation, was initially admitted for seizures and altered mental status under the impression of bacterial meningitis. He had an upper GI bleed during the same hospitalization, and an inpatient upper endoscopy showed a Forrest 1a ulcer in the gastric fundus s/p clipping (Fig 1A). A repeat upper endoscopy three months later showed gastric erythema and a 6 mm non-bleeding healing gastric ulcer in the fundus (Fig 1B). The pathology report of antrum biopsy showed fundic and transitional zone gastric mucosa, mild chronic gastritis without intestinal metaplasia or dysplasia, and the presence of a few atypical lymphocytes. The body biopsy showed fundic/body type gastric mucosa, and findings were compatible with low-grade B-cell lymphoma, favoring extranodal marginal zone lymphoma of MALT lymphoma (Fig 1C). The patient was empirically treated for H. pylori with Bismuth-based quadruple therapy. The patient improved on follow-up with GI. Hematology-Oncology is currently planning for FISH for t(11;18) and/or MYD88 mutation status to assist in the differential, as the H. pylori strain was negative on biopsy. Discussion: Several theories describe pathways for lymphoid proliferation in H. pylori-negative patients, but the exact mechanism has yet to be determined. Currently, it is deemed multifactorial. There is a high incidence of translocation (11;18)(q21;q21) in H. pylori-negative MALT lymphomas is seen. Using radiation therapy for patients with early-stage (Lugano I/II) gastric MALT lymphomas that are negative for H. pylori infection is recommended, with clinical remission rates of up to 100%. Conversely, organ-preserving therapy has no added benefit and surgical treatment is rarely pursued. Therefore, it is recommended to eliminate the presence of H. pylori and evaluate for this translocation. Recent studies have suggested that H. pylori eradication therapy is effective in some proportion of these patients and could be considered a first-line treatment.Figure 1.: A) Upper endoscopy image of Forrest Class 1a ulcer s/p two clips. There is a spurting gastric ulcer with spurting hemorrhage. B) Upper endoscopy of gastric erythema and a 6 mm non-bleeding healing gastric ulcer in the fundus. C) Pathology: Low power view, H&E stain, of antrum biopsy showing fundic and transitional zone gastric mucosa, mild chronic gastritis without intestinal metaplasia or dysplasia, and the presence of a few atypical lymphocytes Immunohistochemistry studies showed atypical lymphocytes CD20+, CD79a+, PAX5+, CD5-, CD10-, BCL6-, BCL2+, CD43+, CyclinD1-, BCL6, and CD10, highlighting very small, scattered, disrupted germinal centers. CD3 and CD5 highlighted numerous admixed T-cells. Ki-67 was overall low (5-10%). Kappa(ish) and Lambda(ish) stains showed that the plasma cells were kappa-restricted, and had low mitotic activity, supporting the diagnosis of marginal zone lymphoma.