Although the lineage-specific ablation of SOX2+ tumor cells or suppression of SOX2 expression in cancers either by genetic means (Table 1) or by anti-cancer drugs (e.g. mithramycin or LSD1 inhibitors) could reduce or halt tumor growth in vitro, these therapeutic options need to overcome a greater challenge in cancer patients in terms of recognizing cancer and non-cancer stem cells because both of them express SOX2. The gene discussed is SOX2; the disease is cancer.