A wide spectrum of inherited cancer predisposition syndromes is associated with the occurrence of tumors of the central and peripheral nervous systems. Constitutional mutations in specific genes, expressing varying degrees of penetrance of the cancer phenotype, are associated with specific patterns of tumor development. These include neurofibromatosis types I and II (NF1, NF2), Gorlin syndrome (PTCH), hereditary paraganglioma syndrome (PGL1, PGL2, PGL3), Turcot syndrome (APC), Rubenstein-Taybi syndrome (CBP) and von Hippel-Lindau disease (VHL). Li-Fraumeni syndrome (LFS) represents another such disorder in which neuronal tumors have been reported. Unlike many other cancer predisposition syndromes, no other clinical congenital anomalies are apparent in LFS, and tumors derived from tissues other than the neural crest are the predominant cancer phenotype.