The different molecular pathways of colonic carcinogenesis are the chromosomal instability pathway, the microsatellite instability pathway inducing errors in DNA mismatch repair and the CpG Island Methylator Phenotype (CIMP). The hypermethylation of CpG islands of genes promoters leads to an over or most frequently under gene expression. CIMP is observed in near 15% of CRC and is associated with specific clinical and pathological features: older patients, female predominance, right colonic involvement, poorly differentiated or mucinous adenocarcinomas. From a molecular point of view, the high CIMP phenotype is strongly associated with the presence of BRAFV600E mutation, the absence of RAS mutation and the presence of microsatellite instability. The prognostic value of CIMP is actually controversial. A recent meta-analysis found that the CIMP phenotype was associated with a poor prognosis. Methylation of some genes promoters as CDKN2A is associated with a poor prognosis.