Colorectal cancer (CRC) is the largest cancer killer in non-smokers in Westernized countries. Susceptibility to CRC can be predicted on the basis of a family history of the disease, particularly when this involves early age of onset. The factors of relevance are age and sex, where both increasing age and maleness are associated with increasing risk. CRC provides an excellent system for the study of the genetic changes which occur during the development of a common human cancer. Most CRCs arise from benign adenomas which develop from aberrant colonic crypts, which means that the developing carcinoma can be observed, removed and studied at all stages from an aberrant crypt focus to metastatic carcinoma. Environmentally sensitive genetic polymorphisms are some of the most recently described CRC-predisposing factors. A functional polymorphism in the methylenetetrahydrofolate reductase gene appears to confer a 50% reduction in CRC risk in the US population.