The majority of clinically defined familial cancer syndromes have been associated with molecular defined hereditary cancer syndromes with known gene mutations in the recent years. Patients with identified mutations should undergo a screening program adapted to the individual risk profile. Prophylactic surgery with resection of the organ at risk is an accepted option for some of the known cancer syndromes (i.e. FAP, medullary thyroid cancer). For HNPCC and hereditary gastric and pancreatic cancer, however, no recommendations regarding prophylactic surgery can currently be given. Prior to performing a prophylactic resection cancer penetrance, diseases associated with the syndrome and the extent of the surgical procedure have to be considered. It seems to be of high importance to keep the perioperative morbidity and mortality as low as possible in preventive surgery; concentrating prophylactic procedures in centers seems therefore to be a reasonable approach.