Eribulin mesylate is a non-taxane microtubule dynamics inhibitor that recently gained Food and Drug Administration approval for late-line metastatic breast cancer (MBC). In this single-arm, multicentre open-label phase II trial Japanese patients pretreated with an anthracycline and a taxane received 1.4 mg/m2 eribulin mesylate (2- to 5-min i.v. infusion on days 1 and 8 of a 21-day cycle). The primary efficacy end point was overall response rate (ORR) by independent review. Patients (N = 80) had received a median of three prior chemotherapy regimens (range 1–5). ORR was 21.3% 95% confidence interval (CI) 12.9–31.8; all partial responses (PRs), stable disease (SD) occurred in 30 patients (37.5%) and the clinical benefit rate (complete response + PR + SD ≥6 months) was 27.5% (95% CI 18.1–38.6). Median duration of response was 3.9 months (95% CI 2.8–4.9), progression-free survival was 3.7 months (95% CI 2.0–4.4) and overall survival was 11.1 months (95% CI 7.9–15.8). The most frequent treatment-related grade 3/4 adverse events were neutropenia (95.1%), leukopenia (74.1%) and febrile neutropenia (13.6%). Grade 3 peripheral neuropathy occurred in 3.7% of patients (no grade 4). Eribulin exhibited efficacy and tolerability in Japanese patients with heavily pretreated MBC.