The epithelial-mesenchymal plasticity, in tight association with stemness, contributes to the mammary gland homeostasis, evolution of early neoplastic lesions and cancer dissemination. Focused on cell surfaceome, we used mouse models of pre-neoplastic mammary epithelial and cancer stem cells to reveal the connection between cell surface markers and distinct cell phenotypes. We mechanistically dissected the TGF-beta family-driven regulation of Sca-1, one of the most commonly used adult stem cell markers. We further provided evidence that TGF-beta disrupts the lineage commitment and promotes the accumulation of tumor-initiating cells in pre-neoplastic cells.