Magnetic resonance-guided focused ultrasound (MRgFUS) utilizes high-intensity focused ultrasound to noninvasively, thermally ablate lesions within the body while sparing the intervening tissues. Magnetic resonance imaging provides treatment planning and guidance, and real-time magnetic resonance thermometry provides continuous monitoring during therapy. Magnetic resonance-guided focused ultrasound is ideally suited for the treatment of extra-abdominal desmoid fibromatosis due to its noninvasiveness, lack of ionizing radiation, low morbidity, and good safety profile. Conventional treatments for these benign tumors, including surgery, radiation, and chemotherapy, can carry significant morbidity. Magnetic resonance-guided focused ultrasound provides a safe and effective alternative treatment in this often-young and otherwise healthy patient population. While there is considerable experience with MRgFUS for treatment of uterine fibroids, painful bone lesions, and essential tremor, there are few reports in the literature of its use for treatment of benign or malignant soft tissue tumors. This article reviews the principles and biologic effects of high-intensity focused ultrasound, provides an overview of the MRgFUS treatment system and use of magnetic resonance thermometry, discusses the use of MRgFUS for the treatment of extra-abdominal desmoid tumors, and provides several case examples.