Independent studies by Vanner et al. (2014) and Boumahdi et al. (2014) reported that SOX2-expressing (SOX2+) tumor cells could drive cancer malignancy by serving as the founding population with the ability to initiate and propagate tumor growth and give rise to the diversity of differentiated cell progenies in different cancer types (Figure 1A and B). This evidence concerns the gene SOX2 and cancer.