There is much evidence suggesting that in cancer there are stem cells that mimic their normal counterparts and have the ability to self-renew as well as produce cells that differentiate into more specific cell types. Therapy aimed at killing the most prominent cancer cells present in a child, often a more differentiated blast progenitor, may or may not kill the stem cells. This leads to major clinical responses in a malignancy but does not offer a cure because the stem cells maintain their ability to proliferate. Increasing molecular technology and discovery have led to an increased understanding of the presence and importance of these cancer stem cells. This symposium will address our current understanding of cancer stem cells in three childhood cancers: acute lymphoblastic leukemia (ALL), acute myelogenous leukemia, and neuroblastoma, with implications for improved therapy.