Abstract: The purpose of this study was to investigate the expression of ZAP-70 in leukemic blasts of 40 newly diagnosed patients of B-cell acute lymphoblastic leukemia (B-ALL) by flow cytometry and to correlate its expression with the clinical and laboratory data as well as the response to induction chemotherapy together with CD20 as a maturational antigen (marker). ZAP-70 was expressed in 47.5% of cases (50% in adults and 45.8% in children). The highest expression was associated with pre and mature subtypes of B-ALL. ZAP-70 was significantly higher among the CD20 and Igμ positive cases, also it was associated with poor response to therapy especially in children, so it may have a prognostic value. Moreover, ZAP-70 could be a candidate molecule for targeted therapies in ALL.