Hereditary cancer syndromes are noteworthy for extensive genotypic and phenotypic heterogeneity, giving rise to the need for care in collection of familial history of cancer of all anatomic sites in extended pedigrees (Vogelstein and Kinzler, 1998; Lynch, 2001), all in concert with genetic counseling (Lynch et al., 2003). This is particularly the case for those rare hereditary disorders which predispose to both colorectal cancer (CRC) and brain tumors. For example, while brain tumors may be an integral lesion in certain hereditary CRC syndromes, CRC always predominates, while brain tumors occur only infrequently even when they are recognized as an essential component of the particular syndrome of concern. When a specific germline mutation is linked to the syndrome’s etiology, confirmation of the etiologic significance of the association of a brain tumor may then be elucidated. Perhaps the best clinical example of this phenomenon is found in the hereditary association of colonic adenomas, CRC, and CNS tumors that is known as Turcot syndrome. This disorder has been found in both familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC) also known as Lynch syndrome.