PURPOSE: To determine the safety of and survival outcomes associated with single-session, whole-liver radioembolization with Yttrium-90 (Y-90)-labelled resin microspheres in patients with nonresectable liver metastases from breast cancer that were refractory to other treatments. MATERIALS AND METHODS: Thirty patients underwent radioembolization with Y-90-labeled resin microspheres infusion in a single-session, whole-liver treatment. All patients had undergone polychemotherapy regimens including at least anthracyclines and taxanes, hormonal therapy, and trastuzumab where applicable. Follow-up data were available for 23 patients. After treatment, the authors assessed tumor response with computed tomography and/or magnetic resonance imaging by using Response Evaluation Criteria in Solid Tumors (RECIST), laboratory and clinical toxicities, and survival. RESULTS: A mean activity of 1.9 GBq of Y-90 was delivered. Follow-up at a median of 4.2 months demonstrated partial response, stable disease, and progressive disease in 61%, 35%, and 4% of patients, respectively. With respect to tumor diameters, imaging revealed a maximum and minimum response of -64.8% to +23.6%, respectively (mean, 29.2%; median, 39.7%). The median follow-up time was 14.2 months. The median overall survival was 11.7 months. The median survival of responders and nonresponders was 23.6 and 5.7 months, respectively, and the median survival of patients with and patients without extrahepatic disease was 9.6 and 16 months. Clinically significant toxicities with the appearance of increasing transaminase level, increasing bilirubin level, nausea and vomiting, gastric ulcers, and ascites occurred in eight of 30 patients. One patient's death was attributed to treatment-related hepatic toxicity. CONCLUSIONS: Single-session, whole-liver Y-90 radioembolization can be performed with an acceptable toxicity profile in patients with liver metastases from breast cancer. Response to radioembolization in these patients is supported by the decrease in tumor size. Further investigation is warranted to prove survival benefit.