The pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is an intriguing issue and is thought to be closely related to Helicobacter pylori infection. Gastric MALT lymphoma is thought to progress from the reactive state to low-grade malignancy and sometimes to high-grade malignancy. In the present study, we examined immunohistochemically the expression of bcl-6 and p53 proteins in gastric MALT and gastric diffuse large lymphoma without low-grade MALT lymphoma component (gastric DLL) to elucidate their role in high-grade transformation of low-grade MALT lymphoma. We detected bcl-6 protein only in the high-grade components in four of eight high-grade MALT lymphoma cases and in four of six gastric DLL cases. In contrast, none of 17 cases of low-grade MALT lymphoma expressed bcl-6 protein (P < .05). p53 protein was detected in the high-grade components in 6 of 8 high-grade MALT lymphoma cases and in 4 of 6 gastric DLL cases, but it was expressed in 2 of 17 cases of low-grade MALT lymphomas. All high-grade gastric MALT lymphomas cases were positive for p53 protein and/or bcl-6 protein. There is a tendency for an inverse relationship between bcl-6 protein and p53 protein. These findings suggest that high-grade transformation of gastric low-grade MALT lymphoma is associated with overexpression of p53 or bcl-6 protein.