For many years, cancer research has focused on the adult stem cells present in malignant tumors. It is believed that current cancer treatments sometimes fail because they do not target these cells. According to classic models of carcinogenesis, these events can occur in any cell. In contrast, the cancer stem cell (CSC) hypothesis states that the preferential targets of oncogenic transformation are tissue stem cells or early progenitor cells that have acquired the potential for self-renewal. These tumor-initiating cells, or CSCs, in turn, are characterized by their ability to undergo self-renewal, a process that drives tumorigenesis and differentiation, which contributes to the cellular heterogeneity of tumors. Herein, we discuss the definitions and properties of CSCs in the major human cancers.