Like their normal counterparts, many tumours are thought to have a hierarchical organization, albeit a disorganized one. Accordingly, the concept of cancer stem cells has emerged, and that these cells are responsible for perpetuating tumour existence. Operationally, cancer stem cells are regarded as prospectively purified cells that are the most effective at tumour initiation in an in vivo assay, usually after xenotransplantation to NOD/SCID mice. The conventional wisdom is that such tumour-initiating cells are rare based upon having to xenotransplant large numbers of human tumour cells into immunodeficient mice to propagate the tumour, but new evidence indicates that perhaps these cells are not so rare, at least in malignant melanoma, if a supportive soil is provided for the transplanted cells along with further restriction of the murine host's immune response.