The Cytochrome P450 (CYP) enzymes constitute one of the biggest gene families and play a vital role in the metabolism of endogenous biomolecules, drugs and xenobiotics. One of the members of this family, CYP2B6, plays a very important role in metabolizing carcinogens and medications. CYP2B6G15631T gene polymorphism reduces CYP2B6 enzyme activity. In this study, we aimed to determine whether any association exists between genetic polymorphism in CYP2B6G15631T and individual susceptibility to acute leukemia. Our study group consisted of 80 acute leukemia patients and 100 unrelated healthy volunteers as a control group. 44 of the acute leukemia patients were diagnosed with acute lymphoblastic leukemia (ALL) and 36 patients with acute myeloid leukemia (AML). Genomic DNA was isolated from peripheral blood and genomic DNA samples were assayed for restriction fragment length polymorphism in the CYP2B6 loci by PCR amplification followed by digestion with BsrI. The data were analyzed statistically employing chi-square and logistic regression analyses. The frequencies of GG genotype (wild type) were 40.9%, 50% and 67% in ALL, AML and control groups, respectively. The frequencies of polymorphic GT genotype (heterozygous variant) were found to be 59.1% in ALL patients, 50% in AML patients and 33% in controls. The TT genotype (homozygous variant) was not observed in either control or leukemia cases. Logistic regression analyses showed a significant correlation between the CYP2B6 G15631T polymorphism (GT) and acute leukemia patients (OR=2.481, 95% CI=1.353-4.551, p=0.003). Our findings indicate that GT genotype may be an important genetic determinant for acute leukemias. According to our knowledge, this is the first report of an association between acute leukemia cases and the CYP2B6 G15631T polymorphism.