Consistent with an autosomal dominant tumor predisposition syndrome, we found that NF1-associated gliomas occurred in patients with a heterozygous germline (or mosaic) mutation/deletion involving one of two NF1 alleles with tumors that developed following somatic inactivation of the remaining wildtype allele through either loss of heterozygosity or a second tumor-acquired mutation. Here, NF1 is linked to glioma.