NRAS wildtype melanomas with NOTCH4-Mut were identified to be associated with prolonged overall survival (OS) in both the discovery (HR: 0.30, 95% CI: 0.11–0.83, P = 0.01) and validation cohorts(HR: 0.21, 95% CI: 0.07–0.68, P = 0.003). This evidence concerns the gene NRAS and melanoma.