Long-standing investigations into the role of diet in colon cancer have generally supported the notion that some aspect of dietary fats acts to promote cancer at this site. Understanding of the chemical behavior of lipids in the colon led to a hypothesis suggesting that depletion of calcium could partly explain the tumor-promoting effects of dietary fat. Calcium levels may control critical intracellular events in the course of proliferation. Lack of availability or loss of calcium may result in abnormalities in the regulation of colonic proliferation. Basic and clinical studies suggest that calcium supplementation reduces colonic proliferation implying a potential reduction in cancer risk. The current evidence supporting calcium as a cancer chemoprevention agent is reviewed.