Identification of the key regulatory molecules in metastasis is crucial for understanding tumor dissemination and for the development of novel interventions. The recent identification of ezrin as a necessary component in the metastasis of osteosarcoma and rhabdomyosarcoma is, therefore, an important advance. Ezrin has been implicated in many roles, for example, as a conduit for signals between metastasis-associated cell-surface molecules and signal transduction components. This suggests that ezrin and, potentially, other members of the ERM (ezrin–radixin–moesin) family have key roles in the coordination of signals and cellular complexes that are required for the successful metastasis of these and other malignancies.