Quite unexpectedly, these BRAF inhibitors were shown to possess the paradoxical effect of activating RAF and downstream ERK in cells with wild-type BRAF including skin keratinocytes, with consequent high incidence of hyper-proliferative disorders, including squamous cell carcinoma, in patients treated with these drugs [3,4,5]. The gene discussed is BRAF; the disease is squamous cell carcinoma.