Here we describe four patients in a multigenerational family carrying a novel heterozygous variant in IKZF3 (NM_012481:c.479 A>G, p.N160S) associated with T and B cell developmental and functional defects, CID, and PJP, as well as CLL (in one patient). The gene discussed is IKZF3; the disease is B-cell chronic lymphocytic leukemia.