Breast cancer cells were recently found to produce syncytin, an endogenous retroviral protein implicated in cell fusion, immune regulation, and nitric oxide synthase expression. To determine whether syncytin has a prognostic role in breast cancer, we investigated a series of 165 premenopausal lymph node-negative women for syncytin expression using an immunocytochemical scoring system. Results were analyzed with the Kaplan-Meier method and with the Cox proportional hazard model. Syncytin expression was observed in 38% of the patients, and the degree of syncytin expression constituted a positive prognostic indicator for recurrence-free survival. In addition, we examined a second series of 54 consecutively operated breast cancer patients of all categories and the results supported the conclusions made from the first study. Thus, syncytin expression constitutes a positive prognostic factor in breast cancer - a phenomenon that may be related to the involvement of syncytin in mediating fusions between breast cancer cells and entodhelial cells.