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Introduction: Brain metastases are diagnosed in approximately 6% to 16% of all metastatic breast cancer patients. Theincidence of brain metastases is much higher for patients with human epidermal growth factor receptor 2 (HER2)-positivebreast cancers, in the range of 25% to 34%. More patients are presenting with uncontrolled brain metastases sincetrastuzumab-based therapy has improved survival in this population. However, treatment options in these patients arelimited after whole brain radiation therapy (WBRT) has failed. Case presentation: In an effort to control brain metastases, three patients who had progression of HER2-positive breastcancer after WBRT received the angiogenesis-inhibiting drug bevacizumab, a humanized monoclonal antibody against thevascular endothelial growth factor (VEGF) ligand. The patients showed clinical improvement and regression of tumorgrowth. After initial diagnosis of brain metastases, patient 1 survived 14 months, patient 2 survived 32 months, and patient3 survived 45 months. Bevacizumab controlled brain metastases for 6, 13, and 19 months, respectively, after progressionon WBRT. Conclusion: This subset of patients with brain metastases and HER2/neu-positive breast cancer clearly responded to ananti-VEGF regimen, suggesting the need for a prospective clinical trial of bevacizumab with lapatinib or otherHER2-targeted therapy in this patient group.