INTRODUCTION: Soft tissue sarcomas are aggressive tumours representing less than 1% of all adult neoplasms. Aim of our study was to evaluate PML value asprognostic factor and as a factor predicting response to alkylatingagents/antracycline-based first line therapy. MATERIALS AND METHODS: 111 patientsaffected by locally advanced and metastatic soft tissue sarcoma were selected.PML expression was evaluated by immunohistochemical analysis in pathologicalsamples and in the corresponding normal tissue from each case. PMLimmunohistochemical results were correlated with prognosis and with radiological response to alkylating agents/antracycline-based first line therapy. RESULTS: PMLexpression was significantly reduced in synovial sarcomas (P <0.0001), inmyofibroblastic sarcomas (P <0.0001), angiosarcomas (P <0.0001), leiomyosarcomas (P =0.003), mixoid liposarcomas (P <0.0001) and in dedifferentiated liposarcomas (P <0.0001). No significant difference was found for pleomorphic sarcoma (31.8[95% CI: 16.7 - 41.0; P =0.21). and pleomorphic liposarcomas (P =0.51). Loss ofPML expression was found to be statistically correlated with TTP (P <0.0001),median duration of response (P =0.007) and OS (P =0.02). No correlation wasobserved between PML expression and treatment efficacy. CONCLUSIONS: PML IHCexpression is downregulated in synovial sarcomas, myofibroblastic sarcomas,angiosarcomas, liposarcoma and leiomyosarcomas and its expression correlated withprognosis.