In the present review, we focused on interactions of CLL cells occurring via the surface B cell receptor (BCR) and dependent on specific molecular features of the BCR itself and/or on the presence of the BCR-associated molecule ZAP-70, or via other non-BCR-dependent interactions, e.g. the CD38/CD31 or CD49d/VCAM-1 receptor/ligand interactions (Table 2). This evidence concerns the gene BCR and B-cell chronic lymphocytic leukemia.