Cancer cells with stem cell-like properties (cancer stem cells) are believed to drive cancer and are associated with poor prognosis. Data from mouse models have demonstrated that integrins, the major cellular receptors for extracellular-matrix components, have essential roles both during cancer initiation and progression, and during cell differentiation in normal development. By presenting an overview of the role of integrins in stem-cell biology and in cancer progression, this Commentary aims to present evidence for a role of integrins in the biology of cancer stem cells. Given the recent interest in the role of integrins in breast-cancer initiation and progression, we focus on the role of the members of the integrin family and their coupled signaling pathways in mammary-gland development and tumorigenesis.