GDP–GTP exchange factors (GEFs) promote the activity of RHO GTPases. Menacho-Márquez et al. have examined the role of VAV family GEFs in squamous cell carcinomas. They found that loss of both Vav2 and Vav3 in mice reduced the formation of carcinogen-induced skin tumours, and identified roles for VAV2 and VAV3 in both tumour initiation and promotion. Mechanistically, VAV2 and VAV3 promoted the proliferation of keratinocytes and the recruitment of inflammatory cells. Loss of either VAV2 or VAV3 alone did not prevent tumours, suggesting that both proteins are required.