Most human CRCs are thought to arise from adenomas (adenomatous polyps) that become dysplastic. Adenomatous polyps form in the colon when normal mechanisms regulating epithelial renewal are disrupted. Surface cells lining the intestine are continuously lost into the bowel lumen due to apoptosis and exfoliation and must be continuously replaced. Typically, proliferation occurs exclusively at the crypt base. As cells move towards the luminal surface, they cease proliferating and terminally differentiate. This ordered process is increasingly disrupted as adenomas increase in size, become dysplastic, and eventually attain invasive potential. Th hypothesis that invasive CRCs develop from intermediate precancerous precursors is supported by pathologic, epidemiologic, and observational clinical data.