Latil et al. have shown that the cell of origin of squamous cell carcinomas (SCCs) controls epithelial-to-mesenchymal transition (EMT) and aggressiveness of these tumours. SCCs derived from hair follicles are much more prone to undergo EMT and have more metastatic potential compared with SCCs derived from interfollicular epidermis. Chromatin and transcriptional profiling of these two different epidermal populations during tumorigenesis identified the gene network and different epigenetic states that control tumour initiation and EMT.