The epithelial-mesenchymal transition (EMT) program has emerged as a central driver of tumor malignancy. The EMT program, which converts epithelial cells into more mesenchymal derivatives, is linked to the acquisition of stem-like properties, suggesting that it plays a major role in generating cancer stem cells. This review summarizes evidence supporting the widespread involvement of the EMT program in tumor pathogenesis and explores the connection between EMT and stem-cell traits. The authors propose that epithelial-mesenchymal plasticity is likely controlled by multiple variants of the core EMT program and highlight the need to understand the various programs and their molecular mechanisms. The EMT program is naturally occurring and essential for development, but its activation in cancer cells can lead to increased tumor aggression and metastasis. The review also discusses the role of EMT in the normal epithelial stem-cell state and its impact on cancer stem cells, as well as the contextual signals that induce EMT in carcinoma cells. Finally, the authors emphasize the importance of understanding EMT and epithelial-mesenchymal plasticity for developing new strategies to detect and treat advanced carcinomas.The epithelial-mesenchymal transition (EMT) program has emerged as a central driver of tumor malignancy. The EMT program, which converts epithelial cells into more mesenchymal derivatives, is linked to the acquisition of stem-like properties, suggesting that it plays a major role in generating cancer stem cells. This review summarizes evidence supporting the widespread involvement of the EMT program in tumor pathogenesis and explores the connection between EMT and stem-cell traits. The authors propose that epithelial-mesenchymal plasticity is likely controlled by multiple variants of the core EMT program and highlight the need to understand the various programs and their molecular mechanisms. The EMT program is naturally occurring and essential for development, but its activation in cancer cells can lead to increased tumor aggression and metastasis. The review also discusses the role of EMT in the normal epithelial stem-cell state and its impact on cancer stem cells, as well as the contextual signals that induce EMT in carcinoma cells. Finally, the authors emphasize the importance of understanding EMT and epithelial-mesenchymal plasticity for developing new strategies to detect and treat advanced carcinomas.