The biological evidence for BRAF-V600E mutations employment as an additional biomarker of anti-EGFR mAb resistance is strong: (i) BRAF is the immediate downstream effector of K-ras in the Ras/Raf/MAPK signalling pathway and (ii) BRAF-V600E activating mutations are 100% mutually exclusive of K-ras mutations in colorectal cancer, implying that the activation of either protein is sufficient for colon tumorigenesis. The gene discussed is EGFR; the disease is colorectal cancer.