Metastatic spread of cancer cells from the primary tumors to distant vital organs, such as lung, liver, brain, and bone, is responsible for the majority of cancer-related deaths. Cancer stem cells are likely to play essential roles in the metastatic spread of primary tumors because of their self-renewal capability and their potential to give rise to differentiated progenies that can adapt to different target organ microenvironments. Investigating the metastatic behavior of cancer stem cells (CSCs) is critical for the development of more effective therapies to prevent or delay the progression of malignant diseases. Animal models have been developed to mimic the multistep process of metastasis to various target organs. In this chapter, I will describe several xenograft methods to introduce human breast cancer cells into nude mice in order to generate spontaneous and experimental metastases. Similar experimental approach can be applied to analyze the metastatic behavior of CSCs derived from other tumor types.