This may help to explain why LGR5 expression has previously been linked with no prognostic value.31,68 Using their CRC tumour organoid library, the Sato group recently demonstrated that CRC organoids (CCO) have preserved hierarchical heterogeneity, as evidenced by inversely correlated LGR5 and KRT20 expression (marking stemness and differentiation, respectively).21 Using elegant lineage tracing experiments, they showed that LGR5+ CRC cells could form both LGR5+ daughters (KRT20−) and LGR5− daughters that acquired KRT20 expression. Here, KRT20 is linked to neoplasm.