Background: Despite the advances in the cure rate for acute leukemia, approximately 25% of affected patients suffer from relapses. Expression of genes for the multiple drug resistance (MDR-1) and breast cancer related protein (BCRP) may confer the phenotype of resistance to the treatment of acute leukemia. Objective: To analyze the expression of the MDR-1 and BCRP genes in new cases of acute leukemia via the real time polymerase chain reaction (RT-PCR) and to determine the correlation between their expression and overall survival. Patients and methods: Total number of patients diagnosed as AML (n = 15), ALL (n = 35) and 20 blood donors as a control group included in this study. The expression of messenger RNA for the MDR-1and BCRP genes by RT-PCR were assessed. Myeloid surface markers as (CD34, CD33, CD13 and CD14) and lymphoid surface markers as (CD3,CD5, CD2, CD4 ,CD8 and CD19)were analyzed by flow cytometry (FACS can, Becton Dickinson, Mountain View, CA, USA). Results: The studied groups with MDR gene, BCRP gene show highly significant difference compared to the control (P0.000). The relation between MDR & BCRP in both AML and ALL groups shows no significant difference. There was a significant difference between BCRP expression in AML, ALL groups (P0.01). No significant difference as regards overall survival between MDR +ve cases and MDR negative cases in AML and ALL. In contrast Overall survival in BCRP +ve cases and BCRP negative cases shows a significant difference between AML and ALL groups (P0.01). No significant difference was detected between O.S in AML (MDR +ve , CD34 +ve) and AML (MDR +ve, CD34 negative). In contrast, O.S between AML (BCRP +ve ,CD34 +ve)and AML (BCRP +ve ,CD34 negative) shows a significant difference (P0.01). The difference between O.S in ALL (MDR +ve, CD34 +ve) and ALL (MDR +ve, CD34 negative) was not significant. In contrast a significant difference was detected between O.S in ALL (BCRP +ve, CD34 +ve) and ALL (BCRR +ve, CD34 negative) (P0.01). Overall survinal in AML group with BCRP +ve (CD13 +ve) shows a significant difference (P0.01). In ALL group the association between (MDR +ve and CD19 +ve) or (BCRP +ve and CD19 +ve) cannot significantly affect the survival. Conclusion: We concluded that the evaluation of the expression of genes for resistance to antineoplastic drugs in acute leukemia upon diagnosis, and particularly the expression of the BCRP gene, may be of clinical relevance.