A 61-year-old male with a 12-year history of CLL (Binet stage B, no cytogenetic aberrations, Zeta-chain-associated protein kinase (ZAP-70) overexpression) and multiple prior treatment regimens (Fludarabine-cyclophosphamide-rituximab (FC-R) protocol, ibrutinib and idealisib) presented with worsening malaise and abdominal pain following the re-initiation of ibrutinib, a Bruton tyrosine kinase inhibitor (BTKI), given for maintenance therapy of CLL. Here, BTK is linked to B-cell chronic lymphocytic leukemia.