A prospective study of 277 cholecystectomy specimens for evidence of isolated epithelial dysplasia of gallbladder mucosa is presented. In addition, 15 cases of primary adenocarcinoma of the gallbladder are retrospectively reviewed with particular reference to the presence of metaplasia and dysplasia adjacent to the infiltrating tumor, in order to establish the relationship between metaplasia, isolated epithelial dysplasia, and adenocarcinoma of the gallbladder. Only one case of isolated epithelial dysplasia was found in the 277 cholecystectomy specimens, and this arose within focal incomplete intestinal metaplasia. In the 15 cases of adenocarcinoma of the gallbladder, benign antral and/or incomplete intestinal metaplasia was found adjacent to the tumor in 11 cases. In 10 cases, dysplasia of this metaplastic epithelium was found in continuity with the tumor. The authors conclude that the most common pathway to adenocarcinoma is via dysplasia of metaplastic gallbladder epithelium.