Colorectal tumorigenesis proceeds through an accumulation of specific genetic alterations. Studies of the mechanism by which these genetic changes effect malignant transformation have focused on the deregulation of cell proliferation. However, colorectal epithelial homeostasis is dependent not only on the rate of cell production but also on apoptosis, a genetically programmed process of autonomous cell death. We investigated whether colorectal tumorigenesis involved an altered susceptibility to apoptosis by examining colorectal epithelium from normal mucosa, adenomas from familial adenomatous polyposis, sporadic adenomas, and carcinomas. The transformation of colorectal epithelium to carcinomas was associated with a progressive inhibition of apoptosis. The inhibition of apoptosis in colorectal cancers may contribute to tumor growth, promote neoplastic progression, and confer resistance to cytotoxic anticancer agents.