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Introduction and Importance: Primary pleomorphic liposarcoma of bone is an exceedingly rare sarcoma., Case Presentation: We herein report the case of a primary pleomorphic liposarcoma of the distal femur in a 20-year-old female patient. Magnetic resonance imaging showed a 25.4-mm medullary necrotic tumor process in the lower third of the distal right femoral meta-diaphysis that was weakly enhanced after gadolinium injection. The patient first underwent an open biopsy. Microscopically, a pleomorphic liposarcoma were suspected. Immunohistochemically, tumor cells expressed the S-100 protein. Fluorescent in situ hybridization showed the absence of MDM2 gene amplification and the absence of EWING/PNET translocation. The diagnosis of primary pleomorphic liposarcoma of the bone was then retained. A wide resection and chemotherapy were performed. The patient died of liver metastasis after 8 months of follow-up., Clinical Discussion and Conclusion: Primary pleomorphic liposarcoma has no specific clinical or radiological findings. Histological diagnosis and molecular study are crucial tools for making an accurate diagnosis., Competing Interests: Declaration of competing interest The authors report no declarations of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)