Recent advances in molecular genetics have identified several genes associated with inherited susceptibility to cancer and have provided a means to begin identifying individuals and families with an increased risk of cancer. This rapid expansion of knowledge about cancer genetics has implications for all aspects of cancer management, including prevention, screening, and treatment. These guidelines specifically address hereditary breast/ovarian cancer syndrome (HBOC), Li-Fraumeni syndrome, and Cowden syndrome. These guidelines were developed understanding that much of our knowledge of how the rapidly emerging field of molecular genetics can be applied clinically is preliminary and that flexibility is needed when applying these guidelines to individual families. © Journal of the National Comprehensive Cancer Network.