The stomach is the extranodal site most commonly involved by non-Hodgkin lymphomas. Diffuse large B-cell lymphoma is the most common histotype category arising in this organ. This is an aggressive lymphoma usually presenting as limited disease, being associated or not to Helicobacter pylori infection and mucosa-associated lymphoid tissue-type areas. Histopathological characteristics are similar to those reported for other diffuse large B-cell lymphomas. It occurs more frequently in males with a median age ranging between 50 and 60 years. With an adequate therapeutic strategy, its prognosis is good, with a 5-year overall survival near to 90%. Conservative treatment with anthracycline-containing chemotherapy, followed or not by involved-field radiotherapy has replaced gastrectomy as standard approach against this malignancy. Several questions on the best treatment remain unanswered. Among others, the role of rituximab, consolidation radiotherapy as well as of more conservative approaches like H. pylori-eradicating antibiotic therapy should be better defined.