Uterine tumors with adipocytic differentiation are very uncommon. Mature adipocytes are sometimes seen as an element of smooth muscle neoplasms, more often as lipoleiomyoma, but also in the rare lipoleiomyosarcoma. Exceptional cases have been reported of various subtypes of liposarcoma associated with uterine smooth muscle tumors with or without adipocytic differentiation. We present a case of pleomorphic liposarcoma arising in a lipoleiomyosarcoma of the uterus. Genomic profiling was performed using a validated next generation sequencing panel covering 410 common cancer genes. Alterations were identified in TP53, PTEN, RB1, FAT1 and TERT. The patient's presentation and clinical course as well as the tumor's morphologic, immunohistochemical and molecular genetic findings are reviewed.