BACKGROUND: Red cells devoid of glycophorin B (GPB)‐borne S, s, and U antigens are classified as an S‐s‐U‐ or S‐s‐U variant (U+var) and can arise from deletion and nondeletion genetic backgrounds. In nondeletion forms of S‐s‐U‐, little information is available on whether the altered GPB gene (GYPB) is expressed in red cells. STUDY DESIGN AND METHODS: Red cells classified as S‐s‐U‐ or S‐s‐U+var were tested with anti‐U, anti‐U/GPB, anti‐He, and anti‐N by hemagglutination. Selected samples were tested by flow cytometry, immunoblotting, and polymerase chain reaction amplification using allele‐specific primers. RESULTS: He (MNS6) was found on 23 percent (20/87) of samples. These and another 21 of the 87 samples were agglutinated by an anti‐U/GPB reagent; this indicated that approximately 50 percent of S‐s‐samples possessed GPB variants. The strength of He varied among the samples. Genomic polymerase chain reaction with allele‐specific primers showed the presence of expected DNA GPB‐like products encoding He. Immunoblotting showed that He was carried on a membrane component with a relative molecular mass indistinguishable from that of GPB. CONCLUSION: The finding of He on S‐s‐ red cells provides direct evidence for the presence of an altered form of GPB in red cells previously thought to be devoid of this glycophorin. Quantitative variation in He antigen expression was observed in a subset of S‐s‐ red cells.