The Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon, also known as NFKBIE gene, which encodes for the Inhibitor of kappa B epsilon IκBε, a negative feedback regulator of NF-κB, is found mutated in 1–3% of CLL patients [35,36,37]. This evidence concerns the gene NFKBIE and B-cell chronic lymphocytic leukemia.