The Authors point out the basis for a better characterisation of colo-rectal cancer and precursory lesions. In fact the etiology of familial adenomatous polyposis (FAP), aberrant crypt foci (ACF), hereditary non polyposis colon cancer syndrome (HNPCC) seems to be correlated to molecular pathology. Therefore the Authors review colo-rectal cancer natural history which frequently appears to be not related to clinical evolution.