Gastrointestinal (GI) malignancies account for a large percentage of the cancer burden in the United States. Although the majority of cancer cases are sporadic, approximately 5% to 10% of cancer results from inherited genetic mutations. There are several hereditary cancer syndromes of the GI tract that have been identified. To date, the genetics of colorectal cancer and its associated hereditary cancer syndromes have been characterized in detail, and effective screening modalities and recommendations have been incorporated into standards of care. Today, scientists are beginning to understand the genetic basis of pancreatic and gastric cancer, and in some cases have identified a number of their associated inherited cancer syndromes. Information about cancer genetics and hereditary cancer syndromes not only will provide advanced practice nurses with knowledge of these diseases but also, more importantly, will provide opportunities to improve patient care by providing patients with treatment options and opportunities for the early detection and prevention of cancer.