Compared to noncarriers, individuals with germline POT1 variants had a 10.5-fold increased odds (95% CI: 2.1-51.7; P = .004) of developing a spitzoid subtype melanoma (complete spitzoid morphology) and a 225.1-fold increased odds (95% CI: 51.7-980.5; P < .001) of having a melanoma with spitzoid morphology involving at least 25% of the tumor. This evidence concerns the gene POT1 and melanoma.