The study investigates the role of epithelial-mesenchymal transition (EMT) in circulating tumor cells (CTCs) from breast cancer patients. Rare primary tumor cells express both epithelial and mesenchymal markers, but mesenchymal cells are more prevalent in CTCs. Serial CTC monitoring in 11 patients suggests a correlation between mesenchymal CTCs and disease progression. In an index patient, reversible shifts between epithelial and mesenchymal phenotypes occurred with each cycle of therapy response and disease progression. Mesenchymal CTCs were found as single cells and multicellular clusters, expressing EMT regulators like TGF-β pathway components and the FOXC1 transcription factor. These findings support the role of EMT in the blood-borne dissemination of human breast cancer. The study also highlights the clinical significance of EMT as a potential biomarker for therapeutic resistance and drug target in breast cancer.The study investigates the role of epithelial-mesenchymal transition (EMT) in circulating tumor cells (CTCs) from breast cancer patients. Rare primary tumor cells express both epithelial and mesenchymal markers, but mesenchymal cells are more prevalent in CTCs. Serial CTC monitoring in 11 patients suggests a correlation between mesenchymal CTCs and disease progression. In an index patient, reversible shifts between epithelial and mesenchymal phenotypes occurred with each cycle of therapy response and disease progression. Mesenchymal CTCs were found as single cells and multicellular clusters, expressing EMT regulators like TGF-β pathway components and the FOXC1 transcription factor. These findings support the role of EMT in the blood-borne dissemination of human breast cancer. The study also highlights the clinical significance of EMT as a potential biomarker for therapeutic resistance and drug target in breast cancer.