The signal transducer and activator of transcription (Stat5) funnels extracellular signals of cytokines, hormones, and growth factors into transcriptional activity in the mammary gland. Postnatal development and functionality of this tissue is synchronized with the reproductive cycle. Consequently, Stat5 involvement in lobuloalveolar development, milk-protein synthesis, or tissue remodeling is dictated by the particular reproductive stage. Latent deregulation of Stat5 activity during the reproductive cycle predisposes the tissue to tumorigenesis at a later stage, when the female is no longer fertile. Accumulating data from studies with mouse models and breast-cancer specimens demonstrate a dual role for Stat5 in this context. It causes tumorigenesis, but delays metastasis progression. Consequently, Stat5 activity in breast-cancer specimens marks a better prognosis for survival. J. Cell. Physiol. 209: 305–313, 2006. © 2006 Wiley-Liss, Inc.