Detection of 19 KRAS mutations (exons 2, 3 and 4) and 13 NRAS mutations (exons 2, 3 and 4) RAS protein is a GTPase and one of the key molecules in the downstream signaling pathway of epidermal growth factor receptor (EGFR). These pathways control cell proliferation, differentiation and apoptosis. Frequency of KRAS and NRAS mutations in colorectal cancer are 36~40% and 1~6% respectively. Most frequent mutations are in exons 2, 3 and 4. RAS mutation is predictive of a very poor response to cetuximab (Erbitux®) and panitumumab (Vectibix®) therapy in colorectal cancer (CRC). The most reliable way to predict whether a colorectal cancer patient will respond to one of the EGFR-inhibiting drugs is to test for activating mutations in the RAS gene. A number of large studies  have shown that cetuximab has significant efficacy in mCRC patients with RAS wild-type tumors. NCCN clearly indicates that all patients with metastatic colorectal cancer should be determined of tumor RAS (KRAS/NRAS) gene status. Patients with any known KRAS or NRAS mutation should not be treated with either cetuximab or panitumumab.