In cancer patients, hypercoagulability is a common finding and it has been associated to an increased risk of venous thromboembolisms, but also to tumor proliferation and progression. In this prospective study, in a large cohort of patients with breast cancer, we aimed to evaluate whether pre-chemotherapy abnormalities in hemostatic biomarkers levels: 1. are associated with breast cancer-specific clinicopathological features; and 2. can predict for disease recurrence. D-dimer, fibrinogen, prothrombin fragment 1+2, and FVIIa/antithrombin levels were measured in 701 early-stage resected breast cancer patients, candidate to adjuvant chemotherapy and prospectively enrolled in the HYPERCAN study. Significant prognostic parameters for disease recurrence were identified by Cox-regression multivariate analysis and used for generating a risk assessment model. Pre-chemotherapy D-dimer, fibrinogen, and prothrombin fragment 1+2 levels were significantly associated with tumor size and lymph node metastasis. After 3.4 years follow-up, 71 patients experienced a recurrence. Cox-multivariate analysis identified prothrombin fragment 1+2, tumor size, and Luminal B HER2-neg or triple negative molecular subtypes as independent risk factors for disease recurrence. Based on these variables, we generated a risk assessment model that significantly differentiated patients at low- and high-risk of recurrence (cumulative incidence: 6.2 vs 20.7%; HR=3.5; p<0.001). Our prospective clinical and laboratory data from the HYPERCAN study were crucial for generating a scoring model for disease recurrence risk assessment in resected breast cancer patients, candidate to systemic chemotherapy. This finding stimulates future investigations addressing the role of plasma prothrombin fragment 1+2 in breast cancer patients' management, and in providing the rationale for new therapeutic strategies.