High-intensity Focused Ultrasound (HIFU) has emerged as a promising noninvasive therapy for malignant bone lesions, both metastatic and primary, mainly for pain palliation. This technology utilizes focused ultrasound energy to induce precise thermal ablation at the periosteum, causing denervation and rapid pain relief typically within 1–7 days, compared to the 2–4 weeks required by conventional radiation therapy (Hurwitz et al., J Natl Cancer Inst 106(5), 2014; Lee et al., J Bone Joint Surg Am 99(18):1572–1578, 2017). Clinical studies demonstrate pain response rates between 60% and 100%, with 63–72% of patients able to completely discontinue analgesic medications (Huisman et al., Int J Hyperth 31(3):251–259, 2015; Baal et al., Skeletal Radiol 50(12):2459–2469, 2021). HIFU treatment can be guided by either magnetic resonance imaging (MR-HIFU) or ultrasound (US-HIFU), with the former offering superior soft tissue contrast and real-time temperature monitoring (Napoli et al., RadioGraphics 33(6):1555–1568, 2013). Beyond pain palliation, growing evidence suggests benefits in local tumor control, with tumor volume reduction up to 50% one month posttreatment, and improvement in bone quality through remineralization (Napoli et al., Invest Radiol 48(6):351–358, 2013). The safety profile is excellent, with major complications occurring in less than 1% of patients (Baal et al., Skeletal Radiol 50(12):2459–2469, 2021). As technology advances, HIFU applications continue to expand, with emerging approaches including integration with other treatment modalities and potential immunomodulatory effects (De Maio et al., Radiol Imaging Cancer 6(1), 2024).