If breast cancer patients are not cured, it is largely because of the fact that the cancer has spread beyond its primary site—the breast—to distant sites, such as, e.g., bone marrow, lung, brain, and/or liver. These secondary tumors are called metastases , and the underlying mechanisms leading to these secondary tumor deposits are complex and still ill understood. In this chapter, we report on how to develop clinically relevant human breast cancer cell line xenografts in severe combined immunodeficient mice. In severe combined immunodeficient mice, metastasizing human breast cancer cell lines were identified by their ability to bind the lectin Helix pomatia agglutinin, which was identified as a marker of metastasis in clinical studies. This model system was created to help to define the rate-limiting steps of the metastatic cascade.