Introduction: The surveillance and treatment of patients with Gardner syndrome is tailored towards early recognition of colonic cancer secondary to intestinal polyposis. However, many Gardner patients suffer from extraintestinal tumors, mostly desmoid tumors, which can be challenging to treat due to invasive growth and frequent local recurrence. The aim of this study was to review our experience in the management of both intestinal malignancies as well as desmoid tumors. Methods: Since 1979, we have been treating a family of 105 descendants with Gardner syndrome from three generations living in a remote valley of the Swiss Alps. Patients with positive APC gene mutations were screened by endoscopy, and colorectal resection was performed upon suspicion of pending malignancy. Desmoid patients with locally resectable tumors were treated by surgery alone, whereas large tumours of the abdominal wall were treated by a combination of brachytherapy (BT) and radiotherapy (RT). Outcome was analyzed regarding length of tumor-free survival, overall mortality, and morbidity arising from both surgery and/or radiotherapy. Results: Of 105 family members, 35 are known to have Gardner syndrome. Preventive colorectal resections were performed in 16 patients (15%), with one death due to subsequent gastric cancer. In 5 patients who denied screening endoscopy, invasive tumors of the colon (3 patients), small intestine and stomach (one patient each) developed. Four of these patients died. In 15 patients a total of 23 desmoid tumors were diagnosed, 10 of which (67%) were located in the mesentery. Nine desmoids (64%) were located within the abdominal wall, and four patients (27%) suffered from desmoids in extra-abdominal locations. Excision alone was performed in nine cases (60%), whereas four patients were treated by a combination of BT and RT. Two other patients (13%) died from non-resectable mesenteric desmoids. Following BT/RT, all three patients were free of recurrence at an average follow-up of 11 months, and no specific local or systemic complications occurred.Conclusions: With adequate screening and surveillance for the development of intestinal neoplasms combined with early resection of pending malignancy, good long-term control of these tumors is achievable. However, Gardner-associated desmoid tumors, with their tendency for local recurrence and invasive growth, remain difficult to treat and determine long-term survival and quality of life in many patients. Our data suggest good local control using brachytherapy as an alternative to resection in large desmoids of the abdominal wall that are not amenable to surgical resection.