Most cancer-related deaths are caused by the hematogenous spread of cancer cells to distant organs and their subsequent metastasis. During the early stages of the metastatic cascade, cancer cells disseminate from the primary site via the lymphatic vessels and/or by hematogenous routes. Circulating tumor cells (CTCs), cancer cells that have disseminated into the systemic circulation, may be a predictor of poor prognosis in several carcinomas. An understanding of the molecular mechanisms involved in the blood-borne dissemination of cancer cells may help to clarify the process of metastasis and provide a powerful and non-invasive approach for anticancer treatments that are tailored to individual patients.