Colorectal cancers, whether sporadic or hereditary, are caused by a defined set of molecular events affecting genes that control proliferation, differentiation and senescence of intestinal cells. There are at least two different pathogenetic pathways for colorectal cancer: the chromosomal instability pathway and the microsatellite instability pathway. These different pathways, however, converge on common pathological entities that have crucial functions in the regulation of normal crypt homeostasis. The activation of Wnt target genes constitutes the primary transforming event in colorectal cancer. Preventive strategies aimed at reversing these changes, or new drug developments targeting these cell populations, should be most efficacious.