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Although childhood acute lymphoblastic leukemia is the most common pediatric cancer, its etiology remains poorly understood. In an attempt to replicate the findings of 2 recent genome-wide association studies in a French-Canadian cohort, we confirmed the association of 5 SNPs [rs7073837 (P=4.2 × 10−4), rs10994982 (P=3.8 × 10−4), rs10740055 (P=1.6 × 10−5), rs10821936 (P=1.7 × 10−7) and rs7089424 (P=3.6 × 10−7)] in the ARID5B gene with childhood acute lymphoblastic leukemia. We also confirmed a selective effect for B-cell acute lymphoblastic leukemia with hyperdiploidy and report a putative gender-specific effect of ARID5B SNPs on acute lymphoblastic leukemia risk in males. This study provides a strong rationale for more detailed analysis to identify the causal variants at this locus and to better understand the overall functional contribution of ARID5B to childhood acute lymphoblastic leukemia susceptibility.