Taxanes are the current first-line treatment for advanced cutaneous angiosarcoma (CAS) for patients who considered difficult to treat with doxorubicin due to high age or comorbidity. However, no effective second-line therapy for such patients has been established.We designed a single-arm, prospective observational study of eribulin mesylate (ERB) administered at a dose of 1.4mg/m2 on days 1 and 8 in a 21-day cycle. Advanced CAS patients previously treated with taxane scheduled for ERB use were enrolled. The primary endpoint was overall survival (OS) and the secondary endpoints were response ratio (RR), progression-free survival (PFS), and toxicity assessment.We enrolled 25 patients and the median OS and PFS were 8.6 and 3.0 months, respectively. Best overall RR was 20% (5/25). Although 16 grade 3 or 4 severe adverse events (SAEs) occurred, all patients recovered. Patients who achieved partial response or stable disease as best response had longer OS than those with progressive disease (median OS: not reached and 3.3 months, respectively, P < 0.001). Patients who did not experience SAEs showed longer OS than those who did (median OS: 18.8 and 7.5 months, respectively, P < 0.05). Patients with distant metastasis had shorter median OS than those with loco-regional disease, but without statistically significant difference (3.6 and 16.1 months, respectively, P = 0.19).ERB showed a promising response rate and is a potential candidate for second-line treatment in CAS patient after taxane. However, the occurrence of SAEs in over a half of the participants, suggests caution about ERB use in elderly patients.