The APC gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. APC promotes rapid degradation of beta-catenin and participates in Wnt signaling as a negative regulator. APC is also involved in other processes including cell migration, cell adhesion, transcriptional activation and apoptosis. Germline defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Disease-associated mutations tend to be clustered in a small region designated the mutation cluster region (MCR) and result in a truncated protein product. Somatic mutations in this gene may be observed in colorectal cancer (CRC), stomach cancer and desmoid tumors. Although APC mutations have been reported in up to 5% of low grade gliomas and up to 13% primary glioblastomas (GBM), evidence regarding their involvement in CNS tumors is still limited. Further studies are needed to explore the clinical value of these mutations in CNS tumors.