Musculoskeletal desmoid tumors can be difficult to characterize and to follow. The rate of regression after radiotherapy is variable, with poor response to chemotherapy and postoperative recurrence being common. Eighteen patients undergoing therapy for proven musculoskeletal desmoid tumors had 52 CT studies, which were assessed to determine the utility of CT in following such patients. Computed tomography was found to offer excellent initial baselines prior to additional treatment and in the early postoperative period and followed the tumor response to treatment. Ultimate tumor response could not be predicted by characteristics of or change in tumor margins, by initial or subsequent tumor CT attenuation, by appearance following intravenous contrast medium, or by tumor location. Decreasing size and stabilization of size in a previously growing lesion were the only reliable signs of response; markedly increasing attenuation heterogeneity suggested but was unreliable as an isolated sign of response.