Embryonic stem (ES) cells are pluripotent stem cells derived from preimplantation stage embryos. ES cells proliferate infinitely while maintaining pluripotency. These properties make them attractive sources for stem cell therapies and regenerative medicine. However, undifferentiated ES cells produce tumors when transplanted, which may preclude their therapeutic usage. It is largely unknown why ES cells can possess tumorigenicity without having chromosomal abnormalities. In this chapter, we introduce the methods to identify genes that play roles in tumor-like properties of ES cells.