Differentiation is a complex multi-step process that affects many biological pathways that regulate the expression of specific genes, and cell proliferation. All adult tissues are made up of lineages of cells consisting of tissue stem cells and their progeny (transit-amplifying cells and terminally differentiated cells). Recent data suggest that cancers arise from rare self-renewing stem cells that are biologically distinct from their more numerous differentiated progeny. Growing evidence suggests that pathways regulating normal stem cell self-renewal and differentiation are also present in cancer cells and cancer stem cells (CSCs). Malignant tumours can be viewed as an abnormal organ in which a small population of tumorigenic CSCs have escaped the normal limits of self-renewal giving rise to abnormally differentiated cancer cells that contribute to tumour progression and growth. This new model has important implications for the study and treatment of cancer.