Cancer stem cells (CSCs) are characterized by self-proliferation, an ability for symmetric/asymmetric division and an ability to propagate cancer in vivo. Contrary to our expectation, CSCs show a quiescent nature, the morphology of small resting cells, resistance to multiple drugs/radiation, and side-population phenotypes distinct from major cancer cells. Research has been focused on overcoming drug resistance, discovery of biomarkers for CSCs, and tailored treatment targeting CSCs. Recently changing concepts of CSCs reflect the genetic heterogeneity, hierarchy of cancer tissue, and evolving dynamic mutations within one tumor. First, multiple CSC clones with different mutations including initiating driver mutations can coexist within one tumor. Second, CSCs stand at the top of the tumor hierarchy during therapy or disease progression, and the proportions of these clones are changing dynamically, depending on the cancer progression. Third, tailored treatments should be not fixed, according to the initial situation at diagnosis, but appropriate treatment should be attempted in accordance with the dynamic properties of CSCs at each stage of cancer.