The immunohistochemical expression of bcl-2 and p53 proteins was evaluated in formalin-fixed, paraffin-embedded surgical specimens from 212 patients with primary gastric lymphoma. bcl-2 protein was found to be expressed in 145 specimens (68%). Among the 179 specimens with B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), bcl-2 positivity decreased significantly as the histological grade advanced; bcl-2 was expressed in 93% of low-grade tumors, 88% of mixed-grade (low-grade with a focal high-grade component) tumors, and 44% of high-grade tumors (Cochran's linear trend test; P<.001). p53 protein expression was detected in 43 of 212 cases (20%). Among the B-cell MALT lymphomas, p53 positivity increased significantly as the histological grade advanced; p53 was expressed in 6% of low-grade tumors, 12% of mixed-grade tumors, and 31% of high-grade tumors (Cochran's linear trend test; P<.001). An inverse correlation was observed between the expression of bcl-2 and p53 in all 212 lymphomas (gamma = -0.531; P<.05) as well as in all 179 B-cell MALT lymphomas (gamma = -0.671; P<.01). Although the bcl-2 expression did not correlate with the patient survival, the p53 positive cases showed a significantly poorer prognosis compared with the p53 negative cases (log-rank test; P<.05). These results suggest that the expression of bcl-2 and p53 may, therefore, be associated with the transition from low-grade to high-grade tumors in primary gastric lymphoma.