Despite the molecular evidence of the centrality of the BcR in CLL, the final proof that the BCR stimulation is crucial in all cases of CLL, regardless of the differences in mutational status, antigenic affinities or strength of autonomous signaling, has come from the impressive and virtually universal efficacy of the therapeutic inhibition of the BcR signaling pathway in CLL patients. Here, BCR is linked to B-cell chronic lymphocytic leukemia.