Background: Lymphoid Enhancer-Binding factor-1 (LEF-1) is a 48-kD nuclear protein that is expressed in pro-B cells and mature T cells but not in mature B cell. LEF-1 binds to a functionally important site in the T-cell receptor alpha (TCR .t ) enhancer and confers maximal enhancer activity; LEF-1 belongs to a family of regulatory proteins that share homology with high mobility group protein-1 (HMG1). Lymphoid Enhancer-Binding factor-1 LEF-1 is sufficient to differentiate CLL/SLL from other small B-cell lymphomas and may serve as a useful tool in the diagnosis of CLL/SLL, LEF-1 is highly associated with CLL/SLL among small Bcell lymphomas and therefore can serve as a useful immunehisto-chemistry (IHC) marker for diagnosis and differential diagnosis of CLL/SLL. Aim of the Study:Our aim is to evaluate the role of Lymphoid Enhancer-Binding factor-1 (LEF-1) expression by flow cytometry in patients with chronic lymphocytic leukemia. Methods and Material:This study was carried out on 45 newly diagnosed B-CLL patients attending the hematology oncology clinic of Tanta University Hospitals. The patients were selected for the study on the basis of standard clinical, hematological and immune phenotypic criteria for diagnosis of CLL, In addition to 15 apparently healthy subjects serving as healthy control group. Subjects included in this study were classified into the following groups: Chronic Lymphocytic Leukemia Group I: Included 45 patients with chronic lymphocytic leukemia.Group I: Healthy Control Group. This group included 15 apparently healthy subjects.Results: There was no significant correlation between LEF-1 expression and age and sex, there was a significant negative correlation between LEF1 expression and Hb and platelet count, there was a significant positive correlation