Our results, supported by a recent study demonstrating the involvement of SIX1 in the expansion of alveolar rhabdomyosarcoma cells and preventing their differentiation [103], show a dual role of SIX proteins in both, the acquisition and the maintenance of the myogenic stem fate, but also in their terminal differentiation through the control of many genes expressed in post mitotic differentiated cells. The gene discussed is SIX1; the disease is rhabdomyosarcoma.