Mutations of MYD88 have been identified in CLL [10], B cell lymphoma [11], [12] and Waldenström’s macroglobulinemia12, which affect several conserved amino acids in the intracellular Toll/Interleukin-1 receptor (TIR) domain (Figure 1A). The gene discussed is TLR4; the disease is B-cell non-Hodgkin lymphoma.