INTRODUCTION: Plasma fibrinogen plays an important role in the pathophysiology of tumor cell invasion and metastases. High plasma fibrinogen levels have been associated with poor prognosis in different types of cancer. In the present study, we evaluated the prognostic significance of the preoperative plasma fibrinogen level in a large cohort of breast cancer patients. MATERIALS AND METHODS: Data from 520 consecutive breast cancer patients, treated between 1999 and 2004, were evaluated. Disease-specific survival (DSS), overall survival (OS), and distant metastasis-free survival (DMFS) were assessed using Kaplan-Meier curves. To evaluate the independent prognostic significance of fibrinogen, multivariable Cox regression models were applied. The influence of fibrinogen on the predictive accuracy was further determined by the Harrell's c-index. RESULTS: Univariable analysis revealed a significant association between an elevated plasma fibrinogen level and DSS (hazard ratio (HR) 1.70, 95% CI 1.07-2.76, p = 0.026) that remained significant in multivariable analysis (HR 1.71, 95% CI 1.02-2.85; p = 0.042). An increased fibrinogen level was also significantly associated with decreased OS in univariable (HR 1.71, 95% CI 1.11-2.64, p = 0.015) and multivariable analysis (HR 1.62, 95% CI 1.01-2.61; p = 0.048). In patients with ER/PR+, HER2- tumors, plasma fibrinogen was associated with DSS in univariable (HR 2.65, 95% CI 1.15-6.14, p = 0.023) and multivariable analysis (HR 3.63, 95% CI 1.37-9.64, p = 0.010). Furthermore, in those patients, the estimated c-index of the multivariable model for DSS was 0.755 without fibrinogen and 0.785 when fibrinogen was added. CONCLUSIONS: An elevated preoperative plasma fibrinogen level may represent an independent prognostic marker for survival in breast cancer patients.