Meanwhile, our understanding of CLL biology greatly improved providing a basis for a better understanding of the biologic role of prognostic markers.10 The pathogenesis of CLL is the result of a complex interplay between i) lymphocytes carrying a restricted repertoire of BCR,11 ii) the mutational status of the variable portion of the immunoglobulin heavy chain (IGHV) gene determining different behaviour of neoplastic lymphocyte in response to antigen stimulation, iii) cell activation and interaction with the microenvironment,12 iv) genetic lesions13 (Figure 1). The gene discussed is BCR; the disease is B-cell chronic lymphocytic leukemia.