New data indicate that BRAF signalling and tumorigenesis is copper (Cu) dependent. The growth of BRAF V600E-transformed cells and BRAF-mediated tumour development in cell-transfer and spontaneous mouse models were found to be markedly decreased after genetic ablation of the Cu transporter 1 (CTR1), which mediates cellular Cu uptake and maintains intracellular Cu levels. A Cu-binding site on MEK1 was identified, disruption of which decreased ERK1/2 activation and BRAF V600E-driven tumorigenesis under normal Cu homeostasis. Importantly, the growth and tumorigenicity of BRAF V600E-mutant or BRAF-inhibitor-resistant cell lines were decreased by Cu chelators. These agents are currently used routinely in the treatment of Wilson's disease, suggesting they could be repurposed as a therapy for BRAF V600E-mutant cancers.