Mutation of the p53 tumor-suppressor gene in exons 4 through 9 was examined in 34 cases of primary advanced gastric cancer using PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) and the results were compared with p53 protein expression as determined by immunohistochemistry (IHC) using a monoclonal antibody(DO-1). p53 protein detected by IHC was observed in 14 cases (41.2%) and genotypic mutation detected by PCR-SSCP in exons 4-9 was observed in 13 cases (38.2%) One case showed an aberrant band on PCR-SSCP both in Exon 7 and Exon 8/9. p53 alteration detected by either IHC or PCR-SSCP was observed in 19 cases (55.9%), but only 8 cases (23.5%) showed both p53 mutation and protein expression. We also tried to obtain the correlation between relative intensity of the shifted bands on PCR-SSCP and percentage of positive cells by IHC, but a significant correlation was not seen between relative intensity of shifted bands on PCR-SSCP and positve cell ratio. A discrepancy between p53 protein expression and p53 mutation is observed in primary gastric carcinomas. The reason for this discrepancy are not apparent. However, examination of gastric carcinomas for mutations in other exons may identify a better correlation with protein overexpression. The results obtained in this study suggest that the negative reaction for p53 immunohistochemistry may not necessarily mean no genetic alteration of the p53 locus.