AbstractThe stem cell transcription factor Sox2 is widely recognized for its many roles during normal development and cancer. Over the last several years, it has become increasingly evident that Sox2 dosage plays critical roles in both normal and malignant cells. The work described in this review indicates that the dosage of Sox2 influences cell fate decisions made during normal mammalian development, as well as cell fate decisions in cancer, including those that influence the tumor cell of origin and progression of the cancer. Equally important, Sox2 dosage is a key determinant in the proliferation of both normal cells and tumor cells, where proliferation is restricted in Sox2high cells. Collectively, the studies reviewed here indicate that tumor cells utilize the fundamental effects of Sox2 dosage to suit their own needs. Finally, we speculate that elevated expression of Sox2 helps establish and maintain tumor dormancy in Sox2‐positive cancers.