Metastasis accounts for the majority of cancer related deaths and the molecular and cellular mechanisms that allow tumor cells to escape the primary tumor site and be able to establish secondary tumors are attractive targets for therapy. A key element in the metastatic spread of epithelial tumors is the epithelial-mesenchymal transition (EMT) process, where adherent epithelial tumor cells detach and become invasive cells with mesenchymal traits. The induction of EMT in cells will also induce stem cell characteristics, and thereby generating so‐called “cancer stem cells” (CSCs). The CSCs have the capacity to escape classical cancer treatment, and subsequently function as a “seed” of a new tumor, either causing relapse or metastasis. The architectural transcription factor HMGA2, which is normally expressed during embryogenesis, is aberrantly re‐expressed in cancers where the expression correlates with tumor aggressiveness. HMGA2 is a Central regulator of stemness and differentiation during embryogenesis, and this has recently also been shown for cancer stem cells.