High-intensity focused ultrasound (HIFU) is a noninvasive treatment that induces complete coagulative necrosis of a tumour at depth through the intact skin. This study was to explore the possibility of using HIFU for the treatment of patients with localised breast cancer in a controlled clinical trial. A total of 48 women with biopsy-proven breast cancer (T(1-2), N(0-2), M0) were randomised to the control group in which modified radical mastectomy was performed, and the HIFU group in which an extracorporeal HIFU ablation of breast cancer was followed by modified radical mastectomy. Short-term follow-up, pathologic and immunohistochemical stains were performed to assess the therapeutic effects on tumour and complications of HIFU. The results showed that no severe side effect was observed in the HIFU-treated patients. Pathologic findings revealed that HIFU-treated tumour cells underwent complete coagulative necrosis, and tumour vascular vessels were severely damaged. Immunohistochemical staining showed that no expression of PCNA, MMP-9, and CD44v6 was detected within the treated tumour cells in the HIFU group, indicating that the treated tumour cells lost the abilities of proliferation, invasion, and metastasis. It is concluded that, as a noninvasive therapy, HIFU could be effective, safe, and feasible in the extracorporeal treatment of localised breast cancer.