OBJECTIVE: Neutrophil extracellular traps (NETs) are associated with poor prognosis and an increased risk of venous thromboembolism (VTE) in metastatic breast cancer (MBC). This study aims to determine whether NETs promote hypercoagulability and if NETs and plasma hypercoagulability markers are biomarkers of survival in MBC. METHODS: Circulating levels of neutrophil extracellular trap (NET) markers and hypercoagulability markers (TAT, fibrinogen, and D-dimer) were assessed in 112 MBC patients before treatment, compared to 55 healthy controls. Stratified by NET levels and plasma TAT, fibrinogen, and D-dimer, the correlation with overall survival was analyzed. The NET procoagulant activity was evaluated using fibrin and purified coagulation complex production assays, and by measuring coagulation time (CT). RESULTS: MBC patients exhibited significantly elevated plasma NET levels compared to healthy controls (all CONCLUSION: Our results highlight the increased release of NETs in MBC patients and reveal that NET formation enhances hypercoagulability and cancer progression. Targeting NETs may be a potential therapeutic strategy to inhibit MBC progression and mitigate thrombotic complications in MBC.