We performed a multicenter retrospective cohort study of eribulin mesylate (EM) use in Italy, to describe the current practice for metastatic breast cancer patients (ESEMPiO) in the real-world. Baseline characteristics, treatment administration and safety were summarized using descriptive statistics. No safety concerns were raised in the population enrolled in the ESEMPiO database and treated in a real-life practice. Median progression-free survival and overall survival were 3.2 and 10.1 months, respectively. EM activity was similar between breast cancer subtypes. In metastatic breast cancer patients treated with EM in ‘real-world’ setting, the clinician-registered outcomes were comparable to those reported in pivotal trials. Furthermore, EM maintained clinical activity and a tolerable safety profile.