The XG blood group system is best known for its contributions to the fields of genetics and chromosome mapping. This system comprises two antigens, Xg(a) and CD99, that are not antithetical but that demonstrate a unique phenotypic relationship. XG is located on the tip of the short arm of the X chromosome with exons 1 to 3 present in the pseudoautosomal region of the X (and Y) chromosome(s) and exons 4 to 10 located only on the X chromosome. Xg(a) demonstrates a clear X-linked pattern of inheritance. MIC2, the gene encoding the CD99 antigen, is found in the pseudoautosomal region of both the X and Y chromosomes. Anti-Xg(a) is comparatively rare, and only two examples of anti-CD99 have ever been identified. Alloanti-Xg(a) is considered clinically insignificant; only one example of autoanti-Xg(a) has been reported, but it resulted in severe hemolytic anemia. Insufficient data exist to determine the clinical significance of anti-CD99. Linkage of XG to several X-borne genes encoding inherited disorders has been demonstrated. CD99 is an adhesion molecule, and high levels are associated with some types of cancer.