Stem cells and cancer are two sides of the same coin. Recent evidence suggests that a subset of cancer cells, known as cancer stem cells, may drive tumor growth and metastasis. Understanding the pathways that regulate stem cell proliferation, self-renewal, survival, and differentiation could lead to better cancer treatments. Cancer stem cells may have evolved to minimize the risk of cancer by limiting the expansion of cells. Some blood cancers and solid tumors may contain a cancer cell hierarchy similar to normal tissues, with cancer stem cells producing progeny with limited replication potential. Cancer often arises in tissues requiring constant cell renewal, such as skin, gut, and blood. These tissues rely on a small population of self-renewing stem cells that generate progenitor cells, which undergo limited mitotic divisions before differentiating. This hierarchical system ensures that only stem cells are long-lived. The balance between self-renewal and differentiation is crucial for maintaining the stem cell pool and generating differentiated cells. Stem cells have unique abilities to self-renew and differentiate. The stem cell niche, a specialized microenvironment, regulates stem cell maintenance and self-renewal. In the Drosophila germline, niche cells provide signals that maintain stem cell identity. The niche also controls the choice between self-renewal and differentiation. Stem cell niches are important in preventing uncontrolled stem cell expansion. Genes that promote self-renewal, such as Bmi1, are likely to be oncogenes. Bmi1 is involved in maintaining hematopoietic stem cells and neural stem cells. In leukemia, Bmi1 is required for the self-renewal of leukemia stem cells. The same molecular pathways that regulate normal stem cells are also used by cancer stem cells. Cancer can arise from either normal stem cells or transit-amplifying cells. Oncogenic mutations may inactivate constraints on normal stem cell expansion or allow transit-amplifying cells to continue proliferating without differentiating. These mutations can lead to the formation of cancer stem cells. Understanding the mechanisms that regulate stem cell self-renewal and differentiation may lead to more effective cancer therapies. The differences between normal and cancer stem cells may reveal new therapeutic targets.Stem cells and cancer are two sides of the same coin. Recent evidence suggests that a subset of cancer cells, known as cancer stem cells, may drive tumor growth and metastasis. Understanding the pathways that regulate stem cell proliferation, self-renewal, survival, and differentiation could lead to better cancer treatments. Cancer stem cells may have evolved to minimize the risk of cancer by limiting the expansion of cells. Some blood cancers and solid tumors may contain a cancer cell hierarchy similar to normal tissues, with cancer stem cells producing progeny with limited replication potential. Cancer often arises in tissues requiring constant cell renewal, such as skin, gut, and blood. These tissues rely on a small population of self-renewing stem cells that generate progenitor cells, which undergo limited mitotic divisions before differentiating. This hierarchical system ensures that only stem cells are long-lived. The balance between self-renewal and differentiation is crucial for maintaining the stem cell pool and generating differentiated cells. Stem cells have unique abilities to self-renew and differentiate. The stem cell niche, a specialized microenvironment, regulates stem cell maintenance and self-renewal. In the Drosophila germline, niche cells provide signals that maintain stem cell identity. The niche also controls the choice between self-renewal and differentiation. Stem cell niches are important in preventing uncontrolled stem cell expansion. Genes that promote self-renewal, such as Bmi1, are likely to be oncogenes. Bmi1 is involved in maintaining hematopoietic stem cells and neural stem cells. In leukemia, Bmi1 is required for the self-renewal of leukemia stem cells. The same molecular pathways that regulate normal stem cells are also used by cancer stem cells. Cancer can arise from either normal stem cells or transit-amplifying cells. Oncogenic mutations may inactivate constraints on normal stem cell expansion or allow transit-amplifying cells to continue proliferating without differentiating. These mutations can lead to the formation of cancer stem cells. Understanding the mechanisms that regulate stem cell self-renewal and differentiation may lead to more effective cancer therapies. The differences between normal and cancer stem cells may reveal new therapeutic targets.