The most damaging change during cancer progression is the switch from a locally growing tumor to a metastatic killer. This switch involves numerous alterations that allow tumor cells to complete the complex series of events needed for metastasis. In considering steps required for successful metastasis, extravasation from blood vessels in target organs is regarded as a critical process. Circulating tumor cells arrested in the capillary beds of different organs must invade the endothelial cell lining of blood vessels and degrade its underlying basement membrane in order to escape into the extravascular tissue where they establish metastasis. This unit describes the most common assay applied to evaluate the metastatic potential of blood-borne tumor cells. The protocol is often called "experimental metastasis", distinct from "spontaneous metastasis", where the tumor cells are first allowed to form a primary tumor in the site of injection and then escape into lymphatic or blood circulation. Cultured tumor cells are injected into the tail vein and allowed to circulate. After 12 to 20 days the recipients are euthanized and the lungs are evaluated for the presence of metastatic tumors.