BACKGROUND: High-intensity focused ultrasound (HIFU) is a new, noninvasive technique with potential to ablate and inactivate tumors. Treatment of solid tumors with HIFU has been reported. In this study, the safety and effects of HIFU in the clinical therapy of malignant bone tumors were assessed. METHODS: Biochemical markers and magnetic resonance imaging (MRI) or positron emission tomography (PET)-computed tomography (CT) were used to evaluate 25 patients with malignant bone tumors before and after HIFU treatment. RESULTS: HIFU resulted in significant improvement in biochemical markers, and no severe complications were observed. After HIFU treatment, 21 (87.5%) patients were completely relieved of pain, and 24 (100%) experienced significant relief. On the basis of MRI or PET-CT, HIFU was effective: For patients with primary bone tumors, 6 (46.2%) had a complete response, 5 (38.4%) had a partial response, 1 (7.8%) had a moderate response, and 1 suffered progressive disease; the response rate was 84.6%. For patients with metastatic bone tumors, 5 (41.7%) had complete response, 4 (33.3%) had partial response, 1 (8.3%) had a moderate response, 1 (8.3%) had stable disease, and 1 suffered progressive disease; the response rate was 75.0%. The 1-, 2-, 3-, and 5-year survival rates were 100.0%, 84.6%, 69.2%, and 38.5%, respectively, for patients with primary bone tumors and 83.3%, 16.7%, 0%, and 0%, respectively, for patients with metastatic bone tumors. The survival rates for patients with primary bone tumors were significantly better than for those with metastatic tumors. CONCLUSIONS: HIFU safely and noninvasively ablated malignant bone tumors and relieved pain. HIFU ablation should be further investigated, as it appears to be successful in the treatment of primary malignant bone tumors. © 2010 American Cancer Society.