When crossed with Tyr::CreER mice and tamoxifen was rubbed on their skin, these mice showed skin hyperpigmentation and naevi with ∼80% developing melanomaSleeping Beauty insertional mutagenesis in this model accelerated melanoma latency and penetrance. Treatment with the BRAF inhibitor PLX4720 resulted in tumour regression followed by relapse, and analysis of transposon insertion sites in these melanomas identified putative mediators of resistance. The gene discussed is BRAF; the disease is melanoma.