Surgical resection was performed on a 47-year-old woman for a retroperitoneal mass that weighed 8.5 kg. Histological examination revealed a myxoid sarcomatous tumor. Because diagnosis could not be determined by immunohistochemistry, attention was focused on MDM2 (murine double minute) gene amplification by fluorescence in situ hybridization (FISH) analysis. The tumor was finally determined to be a dedifferentiated liposarcoma. We experienced a case of a giant retroperitoneal dedifferentiated liposarcoma. FISH analysis was useful for the diagnosis and determination of the therapeutic strategy.