The BRAF-V600E mutation has all the hallmarks of the disease-defining genetic lesion in HCL.19,20,24-37 Indeed, it is clonally and somatically present at diagnosis in almost all patients across the entire clinical spectrum of the disease, including patients presenting with leukemic lymphocytosis or without splenomegaly, and it has been detected in anatomic sites rarely involved by HCL (eg, lymph nodes). This evidence concerns the gene BRAF and hairy cell leukemia.