To determine the role and timing of p53 alteration in gastric adenomas, sequentially biopsied gastric adenomas were immunohistochemically studied for p53 overexpression. From a total of 29 cases, 32 adenomas were endoscopically followed up more than 1 year and used in this study. Immunohistochemically, p53 positivity with diffuse or focal staining was observed in 12 of 32 adenomas. During the follow-up period, only four adenomas transformed to adenocarcinoma, of which three showed p53 positivity by immunohistochemistry. The mutation of the p53 gene in exon 5 through 8 was examined in 18 gastric adenomas including four adenomas with malignant transformation. The PCR-SSCP analysis and DNA sequencing revealed four missense mutations and one silent mutation in five adenomas. The missense mutation was present in three adenomas with diffuse p53 staining and in one adenoma with focal p53 staining. The predominant type of mutation was the G:C to A:T transition. In addition to the p53 gene analysis, Ki-ras gene was also investigated, but no mutation in codon 12 and 13 was found in the adenomas investigated. This study indicated that gastric adenomas might be one of the precursor lesions of gastric cancer but somewhat different from colon adenomas in regard to growth potential, p53 staining pattern and the rate of Ki-ras gene mutation.