Manganese superoxide dismutase (MnSOD) plays an important role in protecting cells from injury due to oxidative stress. We used immunohistochemical techniques to evaluate the expression of MnSOD in specimens obtained from 61 patients with gastric cancer. Immunostaining for MnSOD in tumor cells was compared to that of corresponding normal epithelial tissue. Staining for MnSOD was restricted to the cytoplasm of cells, and overexpression was observed more frequently among the normal mucosa than among tumor cells. Either absent or less intense MnSOD staining was observed in the cells of 44 (72.1%) tumors compared to that of the normal mucosa (group A). MnSOD staining of equal or greater intensity than that observed in the normal mucosa was observed in 17 (27.9%) tumors (group B). There was no association of MnSOD expression with metastatic behavior and prognosis, however decreased MnSOD expression in tumor cells (group A) was correlated with a greater probability of infiltrative type or undifferentiated type adenocarcinomas. Multivariate analysis found that gross appearance (mode of invasion) of the tumor was a significant factor related to MnSOD expression (p<0.05). These findings suggested that variations in MnSOD expression among different types of tumors might occur secondary to cell differentiation and/or proliferation.