Background and Objectives: Surgery is the main treatment for extraabdominal desmoid tumors, but the results of further management remain uncertain. Therefore, a retrospective analysis was undertaken to evaluate the toxicity and efficacy of treatment with interferon-alpha (IFN-␣) ± tretinoin in this setting. Methods: Thirteen patients with extra-abdominal desmoid tumors and a median age of 32 years (range, 15-73) received IFN-␣. Seven of these patients received a combination of IFN-␣ and tretinoin in order to test further enhancement. Results: After a mean observation period of 27 ± 15 months (mean ± standard deviation) under treatment with IFN-␣ ± tretinoin, local control was seen in 11 of 13 patients (85%). Seven patients had no evidence of disease at a mean disease-free interval of 22 ± 18 months; in two patients progressive disease occurred after only 7 and 9 months, respectively, of observation. In another four patients, progression of the desmoid tumor was stabilized. Conclusions: The data of this retrospective, nonrandomized study on therapy with IFN-␣ ± tretinoin suggest that such treatment may be effective in prolonging the disease-free interval of patients after intralesional or marginal surgery. Because of the encouraging response rate, this regimen appears to be another nonsurgical treatment alternative.