The article discusses the importance of epithelial-to-mesenchymal transition (EMT) in cancer metastasis, highlighting several unresolved mysteries and recent advancements in understanding EMT. EMT, a cellular plasticity process initially observed in embryonic development, has been increasingly recognized for its role in cancer progression and metastasis. Despite significant progress, several aspects of EMT remain unclear, including the variety of EMT types, cooperative and collective behaviors, spatiotemporal characterization, and therapeutic strategies. The authors emphasize the complexity of EMT, which includes different types of EMT states, such as partial, intermediate, extreme, and ameboid EMT, each with distinct metastatic potential. They highlight the importance of using comprehensive molecular analysis and cellular properties to define and characterize EMT, rather than relying on a few molecular markers. New technologies like single-cell analysis and lineage tracing have revealed the existence of multiple EMT states and their dynamic evolution during metastasis. The article also explores the implications of EMT in collective and individual cell migration and dissemination, cooperative phenotypes within tumors, and the induction of EMT as a cell population decision-making process. It discusses various strategies for targeting EMT in cancer therapeutics, including inhibiting EMT drivers, limiting cellular plasticity, and pushing cells into extreme EMT states or post-mesenchymal states. Finally, the authors conclude by emphasizing the need for further research to better understand the complexities of EMT and its role in cancer metastasis, as well as the development of reliable biomarkers and therapeutic approaches. They highlight the importance of interdisciplinary efforts, advanced technologies, and a nuanced understanding of EMT regulation for advancing cancer research and treatment.The article discusses the importance of epithelial-to-mesenchymal transition (EMT) in cancer metastasis, highlighting several unresolved mysteries and recent advancements in understanding EMT. EMT, a cellular plasticity process initially observed in embryonic development, has been increasingly recognized for its role in cancer progression and metastasis. Despite significant progress, several aspects of EMT remain unclear, including the variety of EMT types, cooperative and collective behaviors, spatiotemporal characterization, and therapeutic strategies. The authors emphasize the complexity of EMT, which includes different types of EMT states, such as partial, intermediate, extreme, and ameboid EMT, each with distinct metastatic potential. They highlight the importance of using comprehensive molecular analysis and cellular properties to define and characterize EMT, rather than relying on a few molecular markers. New technologies like single-cell analysis and lineage tracing have revealed the existence of multiple EMT states and their dynamic evolution during metastasis. The article also explores the implications of EMT in collective and individual cell migration and dissemination, cooperative phenotypes within tumors, and the induction of EMT as a cell population decision-making process. It discusses various strategies for targeting EMT in cancer therapeutics, including inhibiting EMT drivers, limiting cellular plasticity, and pushing cells into extreme EMT states or post-mesenchymal states. Finally, the authors conclude by emphasizing the need for further research to better understand the complexities of EMT and its role in cancer metastasis, as well as the development of reliable biomarkers and therapeutic approaches. They highlight the importance of interdisciplinary efforts, advanced technologies, and a nuanced understanding of EMT regulation for advancing cancer research and treatment.