Pleomorphic liposarcoma (PLPS) is the rarest and more aggressive subtype of liposarcomas, accounting for 10% of all liposarcomas. The diagnosis should be considered after the detection of multivacuolated pleomorphic lipoblasts in biopsy specimens. Wide-margin resection is the treatment of choice. Complementary treatment options, such as radiation therapy and chemotherapy, are debatable in terms of their contribution to curing patients with PLPS. This article reviews the clinical, histopathological, and molecular characteristics of PLPS and discusses the latest trends in the management, therapeutic strategies, and novel investigations of the subject. [Orthopedics. 2023;46(2):e72-e80.].