Outcomes for triple-negative or hormone-refractory metastatic breast cancer (MBC) are poor and treatment options are limited. Described herein are cases of two women who developed MBC following adjuvant chemotherapy and endocrine therapy for human epidermal growth factor receptor 2 (HER2)-negative ductal carcinoma. Both underwent treatment with fulvestrant, followed by paclitaxel and letrozole or nab-paclitaxel. Following disease progression, both patients started single-agent eribulin mesylate (1.4 mg/m(2) on Days 1 and 8 of a 21-day cycle). The first patient is currently continuing on eribulin at full dose, despite interruption for hip surgery and the presence of grade 1 neuropathy in the hands and feet. The second patient had a partial response with eribulin, which was sustained for 4 months. She was able to tolerate the full dose of eribulin despite slight worsening of the neuropathy that was present at baseline. Eribulin may be a beneficial option for hormone-refractory MBC with extensive treatment experience.