A) Potential describes what cells can do in a permissive environment. The cancer stem cell model, and the transplantation assays (black arrows) on which it is largely based, address the potential of cancer cells to form tumors. B) Fate reflects what cells actually do in a specific environment. In the context of cancer, the question is which cells are fated to contribute to tumor growth and disease progression in their actual environment in the patient. Many of the cells that have the potential to form tumors upon transplantation may not be fated to contribute to disease progression in a particular patient because they are not in a permissive environment. For example, some cancer cells undergo cell death due to hypoxia or immune effector activity. Some of these cells might have the potential to form a tumor if transplanted into another environment, but are fated to undergo cell death in the tumor environment in which they actually reside in the patient. There may also be cells that lack the ability to form a tumor upon transplantation but that are nonetheless fated to contribute to disease progression in the patient, such as if they acquire a new mutation that increases their proliferation. Transplantation assays only assess potential, not fate in a patient, and therefore should attempt to detect the full range of cells with the potential to form tumors. No transplantation assay mimics the environment within patient tissues and such assays are neither designed nor capable of assessing cell fate in patients. Consequently, very little is known about the spectrum of cells fated to contribute to tumor growth and disease progression in patients, or the extent to which it overlaps with the spectrum of cells that can form a tumor upon transplantation.