While paraneoplastic leukemoid reaction (PLR) has been sporadically reported in DDLPS, its coexistence with severe anemia and thrombocytopenia, constituting a severe cytokine release syndrome (CRS), is exceedingly rare and presents a significant diagnostic and therapeutic challenge.<h4>Case presentation</h4>A 56-year-old male with recurrent retroperitoneal well-differentiated liposarcoma presented with high fever, profound leukocytosis (WBC up to 43×10<sup>9</sup>/L), severe anemia (Hb 30 g/L), and thrombocytopenia (platelets 10×10<sup>9</sup>/L), which precluded immediate surgery. This evidence concerns the gene GSTM1 and liposarcoma.