CD86 (B7-2), one of the costimulatory molecules on antigen-presenting cells, plays essential roles not only in autoimmunity and transplantation but also in tumor immunity. The purpose of this study was to investigate whether CD86 gene polymorphism was involved in predisposing an individual to colorectal cancer (CRC). The CD86 +1057 G/A polymorphism was genotyped by performing polymerase chain reaction-restriction fragment length polymorphism in 273 patients with CRC and 292 healthy controls. There were significant differences in the genotype and allele distribution of +1057 G/A polymorphism of the CD86 gene between cases and controls. The +1057 AA genotype was associated with a significantly increased risk of CRC when compared with the GG genotype (odds ratio [OR] = 2.16; 95% confidence interval [CI], 1.31-3.58). Using the G allele as a reference, a significant correlation was detected between the presence of the A allele and a risk of developing CRC (OR = 1.42; 95% CI, 1.12-1.80). Interestingly, the A allele in female patients with CRC was significantly higher than that in male patients after stratified analysis (OR = 1.49; 95% CI, 1.04-2.14). These data suggest that CD86 +1057G/A polymorphism may contribute to genetic susceptibility to CRC in a Chinese population.