Since the first report of the BRAF mutation in human cancer was published in 2002, nearly two decades ago, the significance of BRAF-mutated CRC has been established in clinical practice, changing from being merely a prognostic biomarker marker, via being considered a moderate predictive marker for anti-EGFR therapy and actionable genetic alteration, and toward becoming a targetable mutation. The gene discussed is EGFR; the disease is cancer.