We describe the case of a male subject affected by retroperitoneal advanced, anthracycline-pretreated liposarcoma, who experienced a long, beneficial clinical effect from eribulin treatment. In March 2013, a left, paraortic, retroperitoneal mass was surgically removed and diagnosed as Mdm2-positive dedifferentiated liposarcoma. In June 2015, a CT scan revealed disease progression and first-line epirubicin/ifosfamide treatment was started, followed by epirubicin in monotherapy. In January 2017, following a new disease progression, the patient started a second-line eribulin treatment that went on for about 1 year with no major adverse events. The CT scans performed every 3–4 months showed stable disease. After 13 months of treatment, a CT scan revealed disease progression and 10 days later, the patient died of bowel perforation and peritonitis.