In colorectal cancer, BRAF V600E mutations occur in about 10% of patients [10] and indicate non-response to anti-EGFR therapy with cetuximab or panitumumab as first line treatment for metastatic disease [11], whereas triplet encorafenib + binimetinib + cetuximab was granted FDA breakthrough designation for BRAF V600E colorectal cancer in the second line setting based on results from the phase III BEACON trial [12]. The gene discussed is BRAF; the disease is colorectal cancer.