In this article the epidemiologic, pathologic, molecular, and clinical evidence for the adenoma-carcinoma sequence is reviewed. The authors describe the morphologic evolution of the precursor adenomas, from the earliest discernible abnormality of the colon to adenomas with advanced pathologic features, the factors that determine the risk of progression of adenomas to adenocarcinoma, the molecular events that parallel or underlie the morphologic changes, the outcome of clinical interventions that have tested this hypothesis, and the time frame within which this progression is likely to occur.