Mutations of p53, a tumor suppressor gene, are known to be involved in the pathogenesis of a number of neoplasms. This study investigated the distribution of p53 mutations within both esophageal and gastric adenocarcinomas. The correlation between p53 mutations and an overexpression of p53, which has been reported by other researchers, was also explored. Samples were taken from 17 patients following a surgical resection of the tumor. The patients included 8 cases of adenocarcinoma from the cardia (esophagogastric junction) and 9 cases of gastric carcinoma. Two or three samples were taken from each tumor, plus samples of normal tissue from the patient. Denaturing high pressure liquid chromatography (DHPLC) was employed to detect p53 mutations, and samples found to have mutations were then sequenced. The expression of p53 was determined by immunohistochemistry. DHPLC demonstrated that 37.5% (3/8) of esophageal carcinomas and 44.4% (4/9) of gastric carcinomas have p53 mutations. DNA sequencing showed the same mutation to be present in all of the samples from each tumor, while the corresponding normal tissue was free from mutations (except for 2 cases of polymorphism). The results of immunohistochemistry did not demonstrate a relationship between p53 mutations and the expression of p53 protein, and only 4 of the 7 tumors with p53 mutations showed a positive result. These findings support the hypothesis that p53 mutations are homogeneous throughout a tumor and may thus be a more useful diagnostic and prognostic indicator than the expression of p53, which does not reliably correlate with p53 mutations.