Abstract 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 antiCD99 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. Immunohematology 2011;27:68–71.