Background: A systematic review was undertaken to assess the clinical efficacy of non-invasive high-intensity focused ultrasound (HIFU) ablation in the treatment of breast cancer. Methods: MEDLINE/PubMed library databases were used to identify all studies published up to December 2013 that evaluated the role of HIFU ablation in the treatment of breast cancer. Studies were eligible if they were performed on patients with breast cancer and objectively recorded at least one clinical outcome measure of response (imaging, histopathological or cosmetic) to HIFU treatment. Results: Nine studies fulfilled the inclusion criteria. The absence of tumour or residual tumour after treatment was reported for 95·8 per cent of patients (160 of 167). No residual tumour was found in 46·2 per cent (55 of 119; range 17–100 per cent), less than 10 per cent residual tumour in 29·4 per cent (35 of 119; range 0–53 per cent), and between 10 and 90 per cent residual tumour in 22·7 per cent (27 of 119; range 0–60 per cent). The most common complication associated with HIFU ablation was pain (40·1 per cent) and less frequently oedema (16·8 per cent), skin burn (4·2 per cent) and pectoralis major injury (3·6 per cent). MRI showed an absence of contrast enhancement after treatment in 82 per cent of patients (31 of 38; range 50–100 per cent), indicative of coagulative necrosis. Correlation of contrast enhancement on pretreatment and post-treatment MRI successfully predicted the presence of residual disease. Conclusion: HIFU treatment can induce coagulative necrosis in breast cancers. Complete ablation has not been reported consistently on histopathology and no imaging modality has been able confidently to predict the percentage of complete ablation. Consistent tumour and margin necrosis with reliable follow-up imaging are required before HIFU ablation can be evaluated within large, prospective clinical trials.