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. CD86 + 1057G/A polymorphism (rs1129055) is associated with various diseases. The objective of this study was to investigate the association between CD86 + 1057G/A polymorphism and susceptibility to osteosarcoma in a Chinese population. The CD86 + 1057G/A mutation was detected by polymerase chain reaction-restriction fragment length polymorphism in 205 osteosarcoma cases and 216 age-matched healthy controls. Frequencies of CD86 + 1057 AA genotype and +1057 A allele were significantly increased in osteosarcoma patients than in healthy controls (odds ratio = 2.18, 95% confidence interval, 1.21-3.93, p = 0.008; and odds ratio = 1.43, 95% confidence interval, 1.08-1.88, p = 0.011). Our data suggest that the +1057G/A polymorphism of the CD86 gene is associated with increased susceptibility to osteosarcoma.