Neurofibromatosis type 1 (NF1) is a genetic disorder associated with high rates of neural crest-derived tumors, both benign and malignant. Many series have identified cutaneous melanoma as a rare tumor among cancers occurring in individuals with NF1 disease, but the mucosal location has to date never been reported. In this paper, we report an oral melanoma occurring in a patient with NF1 disorder, diagnosed at a locally advanced stage, successfully managed by definitive external beam radiotherapy, along with a comprehensive literature review on the melanoma-NF1 association.