AC133 antigen is expressed restrictively in the immature subset of the CD34+ cells. Hence, it is expected to be a valuable prognostic marker in acute leukemia. Sixty Egyptian children with acute leukemia were enrolled into this prospective study divided into 2 groups: 30 acute myeloblastic leukemia (AML) and 30 acute lymphoblastic leukemia (ALL) patients. Flow cytometric assessment of AC133 expression was performed on CD34bright blast cells. AC133 was expressed in 66.7% and 40% of AML and ALL patients, respectively. AC133-positive expression was not associated with any of the studied standard prognostic factors. In AML, 80% of patients with poor clinical outcome (relapse or death) were positive for AC133 expression, whereas, all ALL patients who developed resistance as well as those who displayed poor clinical outcome had AC133-positive expression (P<0.05). Patients with positive AC133 expression had significantly shorter overall and disease-free survival times compared with AC133-negative patients in both ALL (P<0.001) and AML (P<0.05) groups. AC133 expression percentage was a reliable poor prognostic marker in ALL patients (P<0.0001). AC133-positive expression is an independent poor prognostic factor in childhood acute leukemia and could characterize a group of patients with resistance to standard chemotherapy, as well as high incidence of relapse and death.