The clinical translation of the significance of cancer "running in families" has become a source of major contention as a result of the explosion of knowledge about cancer causality at the molecular level. At the clinical level, the increasing awareness of the familial and hereditary burden of cancer has contributed heavily to both physician and lay concern about cancer risk. Problems in interpretation of the significance of a cancer family history may arise due to a variety of factors, and even if the physician correctly diagnoses a hereditary cancer-predisposing syndrome there may still be barriers to patient compliance with surveillance and management recommendations. Our purpose is to discuss a variety of potential barriers in the diagnosis and management of patients at increased hereditary cancer risk, drawing on examples from a cohort of approximately 300 families evaluated at Creighton University's Hereditary Cancer Consultation Center over 8 years. Each case was selected because of the presence of one or more clinical, pathologic, molecular genetic, psychosocial, economic, confidentiality, or insurance or employment discrimination factors that had the potential to pose an obstacle in diagnosis or in patient compliance with screening and management recommendations.