KRAS is a small G protein that acts as a transducer in the EGFR signalling pathway. This G protein belongs to the GTPase RAS superfamily and triggers the crucial signalling cascades like the MAPK kinase cascade involved in cell growth, proliferation, differentiation, or survival. These cascades play a key role in tumorigenesis when they are aberrantly activated due to the point mutations  . It is considered one of the most important players in human cancers. Point mutations in KRAS are present in 50% of patients with CRC. BRAF encodes a cytoplasmic serinethreonine kinase that acts immediately downstream of KRAS and MAPK signalling pathway, while its aberrant activation enhances cell proliferation and survival. The incidence of the BRAF mutation in metastatic CRC is only 10% but it is considered a very relevant therapeutic target for CRC management. The concomitant KRAS and BRAF mutations also play a very important role in the therapy as these mutations increase the resistance to the chemotherapy and specifically to the new antibody therapy using monoclonal antibodies against EGFR or VEGFR. Thus, the concomitant presence of the KRAS and BRAF mutations are not only very reliable markers for an early detection of CRC but as well a very good tool for the mCRC therapy management improving the outcome for the patients.