Using four mouse models of squamous skin cancer and limiting dilution serial transplantation, Lapouge and colleagues found that cells from benign papillomas formed tumours in recipient mice at a low frequency and only when cancer-associated fibroblasts or endothelial cells were present in the transplanted mixture. This indicates that there are few cancer stem cells (CSCs) in papillomas, which grow rapidly. Conversely, the number of CSCs increased with tumour invasiveness, indicating that the proportion of CSCs in squamous skin tumours changes as they progress.