A small (approximately 5%) subset of melanomas harbor mutations that affect other sites in the BRAF protein.6 These mutations have variable effects on the catalytic activity of BRAF, but virtually all seem to cause hyperactivation of downstream components in the RAS-RAF-MEK-ERK pathway.10 The pathway is also frequently activated by mutations in Nras, which were detected in 28% of the TCGA tumors.6 Mutations in Nras are mutually exclusive with hotspot (V600) mutations in Braf but they are detected in some tumors with mutations that affect sites in BRAF other than V600. The gene discussed is BRAF; the disease is melanoma.