Gene alterations which have been implicated in colorectal carcinogenesis are characterized by three major mechanisms: chromosomal instability, microsatellite instability, and epigenetic mechanisms (i.e., CpG island hypermethylation). Progress in understanding of these genetic and epigenetic instabilities has led to advances in the individualization and characterization of more homogeneous sub-groups of colorectal tumors with regard to progression, prognosis and response to therapy.