We performed immunohistochemical staining for p53 in 152 endoscopic gastric biopsy specimens, including 39 adenomas, 80 carcinomas, and 33 cases of regenerative atypia. Direct DNA sequencing of exons 5,7 and 8 of the p53 gene was performed on 8 specimens. Nuclear p53 immunoreactivity was observed in 36 of 80 carcinomas, 7 of 39 adenomas and none of the cases of regenerative atypia. Three of the adenomas demonstrated diffuse or focal p53 immunoreactivity. All three cases were associated with severe degrees of epithelial dysplasia, and two of them harbored carcinoma on subsequent polypectomy. Among 6 p53 positive carcinomas and adenomas sequenced, 3 showed DNA mutations, all G:C to A:T transitions. These results indicate that positive p53 immunoreactivity in intraepithelial atypical cells on gastric biopsies represents true dysplasia or carcinoma rather than regenerative atypia.