Cyclin D1 is a key protein involved in cell cycle regulation. A common A870G single nucleotide polymorphism in exon 4 of the cyclin D1 gene (CCND1) has an effect on the transcription of 2 different cyclin D1 messenger RNAs. Correlation between genetic polymorphism of A870G of CCND1 and clinical outcome among patients with acute lymphoblastic leukemia (ALL) has been reported. However, the effect on ALL occurrence remains unclear. To examine the genotypic frequency of CCND1 polymorphism, we performed a case-control study in a Chinese population of 183 children with ALL and 190 healthy controls. The genetic frequency of CCND1 had a significant overall correlation in patients and controls. The AA genotype of CCND1 showed a tendency to increase ALL risk 3.2898-fold compared with the AG + GG genotype (P = .0207). Stratification of patients according to cell type, risk level, and chemotherapeutic response showed significance for the AA genotype in T-cell ALL, ALL with high risk, and no complete remission (P = .047, P = .011, and P = .007, respectively). No gene dosage effect was observed in this study. The results of the present study suggested that CCND1 genetic polymorphism may be related to the occurrence of ALL in a population of Chinese children.