Previous studies already identified AKT and ERK as CD38 targets [28,29] and further reports suggest the involvement of Lyn and BTK in CD38 signaling.[30–32] However, our understanding of the functional consequences of activating these signaling molecules downstream of CD38 is incomplete.[11,33] Our study reveals that SYK acts as a central downstream effector of CD38 signaling and regulates survival-, proliferation-, and migration pathways in CLL. Here, CD38 is linked to B-cell chronic lymphocytic leukemia.