Background:Acute Myeloid Leukemia (AML) is a clonal hematopoietic disorder that may be derived from either an HSC or a lineage-specific progenitor cell. AML is characterized both by a predominance of immature forms (with variable, but incomplete, maturation) and loss of normal hematopoiesis. Single or multiple hematopoietic lineages may comprise the leukemic clone.Increased expression of Cluster of Differentiation 96 (CD96) was shown in several subsequent studies to correlate with poor prognosis and enhanced resistance to chemotherapy. Aim of the study: This work aimed to assess whether the expression of CD96 could be considered as a useful biomarker for the assessment of response to induction therapy in patients with AML. Patients and methods:The study was carried out at as a cohort study at the Clinical Pathology Department on 38 adult AML patients who were admitted to the Medical Oncology Department, in the Faculty of Medicine, Zagazig University Hospitals through the duration between 10\2018 to 10\2019. All patients were undergone full history, clinical examination, laboratory investigations included complete blood count, bone marrow aspiration and examination, liver and kidney functions, and LDH. Virology report including (HCVAb, HBsAg, and HIVAb). PT, aPTT. ESR and measuring of CD96 expression. Results:CD96 was expressed in 16/38 patients (42.1%).We found a significant positive correlation between CD96 expression and BM blast cells percentage.Only thirty-one % of patients with CD96+ve expression respond to the induction therapy, while 77.3% of patients without CD96 expression showed a response to induction. There was a statistically significant increase in the CD96+ve expression patients in the non-responder group compared to the responders.The median time of disease-free survival was longer in –ve CD96 patients compared to +ve CD96 patients (7 months and 3 months respectively). Conclusion:CD96 is frequently expressed in AML patients. CD96+ve expression is significantly associated with some poor prognostic markers like, increased BM blasts percentage, leukocytosis, and elevated LDH.Expression of CD96 is associated with less response to induction therapy and lower median time of disease-free survival.