Invadopodia are a subset of invadosomes that are implicated in the integration of signals from the tumor microenvironment to support tumor cell invasion and dissemination. Recent progress has begun to define how tumor cells regulate the plasticity necessary for invadopodia to assemble and function efficiently in the different microenvironments encountered during dissemination in vivo . Exquisite mapping by many laboratories of the pathways involved in integrating diverse invadopodium initiation signals, from growth factors, to extracellular matrix (ECM) and cell–cell contact in the tumor microenvironment, has led to insight into the molecular basis of this plasticity. Here, we integrate this new information to discuss how the invadopodium is an important conductor that orchestrates tumor cell dissemination during metastasis.