The discovery of BRAF-V600E as the genetic cause of HCL,20 the development of oral BRAF or MEK inhibitors for BRAF-V600E–positive metastatic melanoma,72 and the preclinical studies strongly supporting the use of these inhibitors in HCL21 provide an important new approach to the therapy of patients with relapsed or refractory HCL. This evidence concerns the gene BRAF and hairy cell leukemia.