Most colorectal cancer arises from epithelial polyps. Polyps can be the result of acquired, germline, or inflammation-associated mutations in colonic stem cells (CSC). Their incidence and risk of progression are determined by factors that modify the baseline rate of spontaneous mutations occurring in CSC. In sporadic polyps, factors are primarily environmental; in individuals with germline mutations, it is the specific mutation, and in inflammation-associated polyps, it correlates with the extent, duration, and severity of the process. The different clinicopathologic and molecular genetic abnormalities underlying the different types of polyps are discussed.