Four hundred and ninety-two eoCRC (20.7%) and 1411 aoCRC (16.4%) patients had left-sided primaries with wild-type BRAF, NRAS, and KRAS. Given the recently reported observation that eoCRC patients with KRAS wild-type left-sided primary tumors may not benefit from first line EGFR inhibition, we explored the potential role of negative hyperselection (defined as the presence of at least one pathogenic or likely pathogenic point mutation in any of the following genes within a tumor: KRAS, NRAS, BRAF (only V600E), AKT1, ERBB2, PIK3CA (exons 9 and 20), PTEN, ALK1, or ERBB2 amplification). The gene discussed is BRAF; the disease is neoplasm.