Like stem cells, cancer cells are able to proliferate indefinitely. There is increasing evidence that the clonal population of neoplastic cells exhibit marked heterogeneity with respect to proliferation and differentiation and cancer cells arise in cells with the characteristics of stem cells. This hypothesis that a subset of cells drives tumorigenesis suggests that targeting elimination of the stem cell-like population of cancer cells is a viable therapeutic strategy. Since in some cases, it is the absence of markers that are characteristic of a cancer stem cell population, both positive and negative markers may be employed to identify these cells. Classical developmental signaling pathways, which are implicated in oncogenesis, are also associated with regulation of stem cell self-renewal and provide yet more areas of focus for understanding cancer stem cell biology.