Seven single nucleotide polymorphisms (SNPs) were genotyped in 535 Brazilian children (158 with acute lymphoblastic leukemia [ALL], 74 with acute myeloid leukemia [AML] and 303 controls). The subjects were classified as fast or slow acetylators based on their genotypic variants. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals. N-acetyltransferase 2 (NAT2) SNP 341T > C frequency was higher among both leukemia subtypes compared to controls. There was also a significant difference in the frequency of SNP 590G > A in AML (OR, 1.57, 1.07-2.30). The haplotypes *14A, *5A and *5C conferred an increased risk in cases of ALL, while *14E, *6B and *6F conferred an increased risk for AML. An age-dependent analysis demonstrated that the NAT2 slow-acetylators conferred an increased risk association with leukemia in children ≤ 1 year old (OR, 7.91, 3.87-16.16) and also in older children (1 ≥ 10 years old) (OR, 1.53, 1.01-2.31). However, in this latter group the magnitude was reduced. The results demonstrate that the different NAT2 haplotypes contribute to the risk of either ALL or AML.