BACKGROUND: The optimal treatment of primary gastric large-cell non-Hodgkin's lymphoma (PGL) has not been defined. Recent studies have suggested that organ-preserving treatment produces the same results as surgical treatment. METHODS: We retrospectively reviewed the data of 88 patients diagnosed with PGL between 1995 and 2003 at Chang Gung Memorial Hospital. Sixty-two patients received chemotherapy (CT), three received CT followed by radiotherapy (CT+RT), three received surgery (ST), 14 received surgery followed by CT (ST+ adjuvant CT), one patient received ST followed by radiotherapy (ST+RT), one patient received radiotherapy (RT) alone, one received eradication therapy for Helicobacter pylori only and 3 patients received no further therapy after diagnosis. RESULTS: Of the 81 patients who received endoscopic biopsy of gastric lesions, the diagnosis of PGL could be made in all but one. Seven patients were diagnosed by pathology after ST without preoperative pathologic diagnosis. The complete remission rate was 77.3%. The 5-year overall survival (OS) and disease-free survival (DFS) were 50.0% and 81.6%, respectively. There was no difference in OS (p = 0.4051) and DFS (p = 0.8519) between patients receiving mainly CT (CT or CT+RT) and those receiving primary surgery (ST, ST+ adjuvant CT or ST+RT). We found that poor performance status (p < 0.0001), elevated beta2-microglobulin level (p = 0.0082) and no CT (p = 0.0002) had adverse effects on OS. CONCLUSION: The present data show that CT should be the primary treatment for patients with PGL if the diagnosis can be made with endoscopic biopsy.