The study was based on 58 (40 males, 18 females) consecutive, previously untreated CLL, 7 HCL (5 males, 2 females), 23 CD5 negative LPD (15 males, 8 females) and 12 multiple myeloma (8 males, 4 females). Mean age of CLL, HCL, CD5 negative LPD and multiple Abstract CD26/dipeptidyl peptidase IV (DPPIV) is a multifunctional membrane protein and it is strongly upregulated in activated B-cells. We aimed to evaluate CD26 expression in mature B cell neoplasms, and its prognostic role in B cell chronic lymphocytic leukaemias (B-CLL). CD26 expression was evaluated by flow cytometry in various B cell neoplasms. CD26 expression was high in MMs and HCLs, variable in B-CLLs and in CD5neg B-CLPDs. Kaplan-Meier curves revealed a significantly shorter progression free survival (PFS), and lymphocytic doubling time (LDT) in the CD26 high expression group (p=0.014, 0.024 respectively). High CD26, CD38 and/or ZAP70 showed significantly shorter PFS, (p=0.020, 0.022 respectively) and LDT (p=0.024, 0.024 respectively) when compared to both low expression CD26, CD38 and/or ZAP70. CD26 expression may identify subsets of B-CLL patients with an unfavorable clinical outcome, thus suggesting its potential role as a marker in a future routine cytofluorimetric panel for B-CLLs.