The process of CTC metastasis. Cancer cells with localized invasion require epithelial mesenchymal transition (EMT), by which adherent cancer cells achieve the ability to migrate, as well as with the loss of integrity of the basement membrane (BM) and the extracellular matrix (ECM). The process permits some metastatic cancer cells to intravasate into the blood. CTCs interact with the microenvironment in the circulation. Finally, only a small proportion of CTCs with the ability to metastasize, or those with traits similar to those of cancer stem cells, are thought to extravasate to distal organs and develop macrometastases. Genetic and molecular analysis of these rare cells may provide a novel tool for evaluating their biological and clinical relevance.