PURPOSE: Variable changes occur in the progression from normal gastric epithelium to cancer, including many tumor, tumor suppressor and DNA repair genes, as well as growth factor and its receptors. The mutation and protein expression of the p53 gene may be useful prognostic factors, but their significance is still uncertain. METHODS: Specimens from 296 gastric cancer patients, treated by a curative gastrectomy, between March 1999 and April 2001, at Kyungpook National University Hospital, were used. The p53 gene mutation was assessed using a polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, and the overexpression of tumor p53 protein using immunohistochemistry. The correlation between the results and clinicopathological parameters were then analyzed. RESULTS: The mutation and protein overexpression of the p53 gene were shown in 61 (20.6%) and 124 (41.9%) tumors, respectively. Of the 61 cases with a p53 mutation, 43 (70.5%) showed overexpression of the p53 protein, and of the 235 without mutation of the p53 gene, 81 (34.5%) had no overexpression of the p53 protein, and also showed statistical significance (P< 0.001). The mutation and protein overexpression of the p53 gene showed no significant differences according to age, gender, stage, location and gross type, but of the 138 intestinal and 128 of the diffuse types, 33 (23.9%) and 18 (14.1%) cases, respectively, showed p53 mutation (P=0.027); whereas, of the 150 well differentiated and 142 poorly differentiated tumors, 75 (50%) and 18 (33.8%), respectively, showed overexpression of the p53 protein. Also, of the 138 intestinal and 128 diffuse types, 71 (51.4%) and 43 (33.6%) showed overexpression of the p53 protein. There were no significant differences in the 5 year survival according to the mutation and protein overexpression of the p53 gene. CONCLUSION: The mutation and protein overexpression of the p53 gene, as assessed by PCR-SSCP and immunohistochemistry, respectively, showed a statistically significant correlation, but had little value as prognostic factors following a curative gastrectomy.