The MNS blood group antigens are expressed in the RBC membrane on glycophorin A (GPA), glycophorin B (GPB), or combinations of both. GPA expresses the M or N antigen, whereas GPB expresses the S or s antigen and the N antigen ('N'). Both glycophorin genes (GYPA and GYPB) are located on the long arm of chromosome 4 and share 95 percent sequence identity. This high degree of sequence identity, together with the rare involvement of a third homologous gene (GYPE), provides an increased chance of recombination, resulting in hybrid molecules that often carry one or more novel antigens. Some of the antigens in the MNS system result from a single nucleotide substitution. The MNS blood group system now consists of more than 40 distinct antigens. This review summarizes the molecular basis associated with some of the antigens in the MNS blood group system.