To address this gap in understanding in CLL and to characterize the clinical significance of recurrent E571 XPO1 mutations, we conducted a multi-center retrospective analysis on a large number of CLL cases (N = 1286), and identified 72 leukemia-cell samples (~ 6%) harboring a nonsynonymous mutation in XPO1 at E571, resulting in an amino acid substitution of E→K in 59 (82%), E→G in 12 (17%), or E→A in 1 (1%) of the cases with XPO1 mutations. The gene discussed is XPO1; the disease is leukemia.