The chapter discusses the role of circulating tumor cells (CTCs) in cancer metastasis and the significance of DNA methylation in their formation and dissemination. CTCs are crucial for the spread of cancer from the primary site to other parts of the body, and recent advancements in technology have enhanced our understanding of the mechanisms behind this process. DNA methylation, which regulates gene expression and chromosome stability, plays a critical role in carcinogenesis. The review covers various processes contributing to CTC formation, including epithelial-mesenchymal transition (EMT), immune surveillance, and colonization. It also explores how DNA methylation modifications within CTCs impact these stages of dissemination. The chapter highlights the potential clinical implications of these epigenetic changes, such as identifying new biomarkers for early detection, prognosis, and targeted therapies. Understanding these mechanisms can bridge the gap between basic research and clinical application, offering new avenues for improving patient outcomes.The chapter discusses the role of circulating tumor cells (CTCs) in cancer metastasis and the significance of DNA methylation in their formation and dissemination. CTCs are crucial for the spread of cancer from the primary site to other parts of the body, and recent advancements in technology have enhanced our understanding of the mechanisms behind this process. DNA methylation, which regulates gene expression and chromosome stability, plays a critical role in carcinogenesis. The review covers various processes contributing to CTC formation, including epithelial-mesenchymal transition (EMT), immune surveillance, and colonization. It also explores how DNA methylation modifications within CTCs impact these stages of dissemination. The chapter highlights the potential clinical implications of these epigenetic changes, such as identifying new biomarkers for early detection, prognosis, and targeted therapies. Understanding these mechanisms can bridge the gap between basic research and clinical application, offering new avenues for improving patient outcomes.