Colorectal cancer (CRC) is not a single disease, but a group of wide spectrum of heterogeneous diseases, and tumors with similar clinicopathological features may react differently to treatments and have diverse prognosis. So complementary risk evaluation, or based on molecular biomarkers to further stratify colorectal cancer beyond TNM staging is necessary. Understanding mechanism of carcinogenesis is good for subtyping colorectal cancer as well as drug development. So far, 3 major pathways are thought to be related to CRC carcinogenesis, chromosome instability, microsatellite instability and CpG island hypermethylation. High throughput profiling enables to study the molecular basis for CRC more comprehensively and systemically. Several studies have defined 3-6 subtypes. Colorectal Cancer Subtype Consortium has made consensus to divide CRC into 5 subtypes based on pool analysis of available profiling data. Further validation is ongoing. There are only a few biomarkers which can be applied in daily practice, including MSI, RAS, BRAF, PI3KCA and HER2.