The correlation of p53 protein expression and p53 mutation of 33 gall-bladder carcinomas was studied according to the depth of invasion and grade of cytological atypia. Overexpression of p53 protein was detected by immunostaining in seven (70.0%) of 10 intramucosal and in 16 (69.6%) of 23 invasive carcinomas. p53 mutation was detected in five (71.4%) of the seven intramucosal carcinomas with overexpression and in eight (50.0%) of the 16 invasive cancers with overexpression and in one (10%) of the 10 non-overexpressing carcinomas at exons 5-8 by nested polymerase chain reaction-single-strand conformation polymorphism. The overexpression of p53 protein was present in nine (56.3%) of 16 low-grade carcinomas and in 14 (82.3%) of 17 high-grade carcinomas. In cases of overexpression, p53 mutation was detectable in four (44.4%) of nine low-grade and in nine (64.3%) of 14 high-grade carcinomas. In total, p53 mutation was verified in 56.5% (13/23) of cases involving protein overexpression and in 10% (1/10) of cases of non-overexpression. The sensitivity of p53 mutation was 56.5% (13/23), the specificity was 90.0% (9/10) and the validity was 1.47. In conclusion, our study indicates that p53 protein overexpression correlates well with gene mutation and that p53 alteration may be related to increasing grade of cytologic atypia of carcinomas.