Somatic NF1 pathogenic mutations in tumours occur in several settings: In NF1 patients, a second NF1 hit occurs in NF1 associated nerve sheath tumours besides a germline NF1 pathogenic variant (first hit) and leads to biallelic inactivation of NF1 following the Knudson two-hit hypothesis. The gene discussed is NF1; the disease is neoplasm.