These surprising results are consistent with a recent report from Toshiro Sato’s group who lineage-traced LGR5+ (leucine-rich repeat-containing G-protein coupled receptor 5) cancer stem cells and KRT20+ (keratin 20) differentiated cells in murine CRC xenografts.6 In agreement with our findings, Sato and colleagues observed that following elimination of LGR5+ cancer stem cells, KRT20+ cells de-differentiated and acquired cancer stem cell features. The gene discussed is KRT20; the disease is colorectal carcinoma.