Cancer is a genetic disease in which the clonal accumulation of genetic alterations confers a cell with the malignant characteristics of uncontrolled growth, local invasiveness, and metastastic potential. Studies of colorectal cancer and its precursor lesion, the adenomatous polyp, have served as the cornerstone in advancing knowledge of cancer molecular genetics. The past 30 years have ushered in an era of revolutionary increases in understanding colorectal cancer genetics. In the future, it is hoped that the tremendous recent gains made in understanding colorectal cancer genetics will allow for significant, tailored chemoprevention and treatment of this common malignancy.