Transforming growth factor-β (TGF-β) is a multifunctional polypeptide that regulates cell growth, differentiation, and extracellular matrix formation. Studies on genetically engineered animal models have demonstrated that TGF-β-mediated signaling pathway plays a critical role in both normal development and tumorigenesis of the breast. In pathogenesis of breast cancer, the role of TGF-β appears featured with growth-inhibitory effects at early stages of carcinogenesis, but aggressive oncogenesis with transition to more advanced malignant states. The TGF-β signaling pathway is also tissue-context and ligand content-dependent. Therein, therapeutic modulation of TGF-β signaling may be a multifactorial event.