Autoimmune and microbial-induced immune reactions are associated with lymphomagenesis, particularly of extranodal marginal zone B-cell lymphomas. This report presents a case of Helicobacter pylori-negative gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the setting of Sjögren syndrome and Hashimoto thyroiditis treated with primary involved-field radiotherapy. This report describes etiologic data, diagnostic and treatment considerations, and sophisticated radiation therapy techniques aimed at reducing long-term toxicity in this indolent disease.