Advanced CRC often harbor several mutations, including KRAS, NRAS, and BRAF mutations, as well as microsatellite instability (MSI)/mismatch repair (MMR) status and other oncogenic pathway dysregulations, which confers resistance to first-line treatment of advanced CRC, including the targeted therapies, monoclonal antibodies targeting anti-epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR). The gene discussed is EGFR; the disease is colorectal carcinoma.