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Heritable Gastrointestinal Cancer Syndromes. Although almost all gastrointestinal cancers develop from sporadic genomic events, approximately 5% arise from germline mutations in genes associated with cancer predisposition. The number of these genes continues to increase. Tumor phenotypes and family history provide the framework for identifying at-risk individuals. The diagnosis of a hereditary cancer syndrome has implications for management of patients and their families. Systematic approaches that integrate family history and molecular characterization of tumors and polyps facilitate identification of individuals with this genetic predisposition. This article summarizes diagnosis and management of hereditary cancer syndromes associated with gastrointestinal cancers.