Pleomorphic liposarcoma is the least common but most aggressive subtype of liposarcoma. Tumors most commonly arise in the deep soft tissues of the extremities in adult patients. Pleomorphic liposarcoma has no specific immunohistochemical or molecular genetic features, and the presence of lipoblasts remains the sole diagnostic criterion. Diagnostic challenges include the identification of lipoblasts, which are often scarce or focal, and the distinction from other pleomorphic sarcomas, including dedifferentiated liposarcoma with homologous lipoblastic differentiation. This review provides an updated overview of the clinicopathologic features of pleomorphic liposarcoma, with discussion of its morphologic variants, differential diagnosis, and the role of small biopsy samples.