ZAP-70 expression has been clinically and biologically linked to aggressive features in CLL, but its regulation is still largely unknown; interestingly, we showed that the proliferative fraction of CLL cells from the PB was markedly enriched in ZAP-70 positive cells, and that the herein described co-culture system induced the expression of ZAP-70 in proliferating cells. This evidence concerns the gene ZAP70 and B-cell chronic lymphocytic leukemia.