In colorectal cancer (CRC), genetic alterations are involved in disease progression from adenoma to carcinoma and metastatic disease. Three different carcinogenesis mechanisms exist: chromosomal instability phenotype (CIN), microsatellite instability phenotype (MSI) and the hypermetylator phenotype (CIMP for CpG Island methylation phenotype). These molecular alterations lead to signal transduction dysfunction, and signaling pathways alterations are involved in cancer mechanisms, such as EGFR pathway, WNT/APC pathway, TGFB pathway and p53 pathway. Recently, molecular signatures have been established, allowing distinction of 4 different types of CCR. Finally, circulating biomarkers are investigated for molecular characterization.