Although the incidence of colorectal cancer in Iranian older age subjects is currently very low compared to Western population, the younger generation is experiencing an accelerated rate approaching the Western rates and the burden of disease will increase dramatically in near future. The high frequency of positive family history of colorectal cancer in Iranian patients indicates that a significant number of colorectal cancers in Iran arise in family members and relatives of colorectal cancer patients. It is clear that the familial clustering of colorectal cancer is more often seen in younger probands and cancer located in the right side of the colon. These epidemiologic findings call for a broader attempt to promote public awareness and screening strategies in those families with a member affected by colorectal cancer, especially at younger age or with proximal tumors. Based on our present understanding, the possibility of preventing or curing most colon and rectal cancers is now plausible. The molecular biology of colon cancer has been the subject of many researches and is better understood than those for any other solid cancer and have established an important example for cancer research. It is now clear that colorectal cancer develops as the result of genetic and epigenetic alterations that lead to malignant transformation of normal mucosa. In spite of these scientific progresses and the fact that screening can reduce the rate of death by detecting early cancer or premalignant polyps, the rate of screening is very low globally and negligible in Iran and many other developing countries which is due to cost, resistance by physicians, patients, and the healthcare system. In Iran screening should at least be started in family members at earlier age with colonoscopy as the preferred modality of screening method.