In search of potential prognostic markers, we analyzed a large series of tissues of Barrett's esophagus and samples of adenocarcinomas arising in the terrain of Barrett's esophagus for TP53 gene mutations by direct sequencing of exons 5 to 9 of the TP53 gene. While 9 of 21 adenocarcinomas tested (42.9%) contained a TP53 mutation, none of 24 samples from Barrett's esophagus were mutated. This observation suggests that TP53 gene mutation may be a relatively late event in the progression from nondysplastic Barrett's esophagus to adenocarcinoma of esophagus. Therefore, TP53 gene mutations alone are not likely to represent a widely useful prognostic marker of the risk of progression to malignancy, at least not in Barrett's esophagus without dysplasia.