The HLA-B locus discloses a higher number of alleles and more complex serologic patterns than those observed for the HLA-A locus. In this article we describe the molecular structure and serologic details of a novel HLA-B allele, B * 1303. B * 1303 has been serologically defined as a B21 Bw4-associated molecule, whereas its primary structure is closely related to B13 alleles. In fact, only three nucleotide and two amino acid substitutions were found with respect to the Caucasian B * 1302 allele. In contrast, there were 10, 14, and 16 amino acid substitutions when compared to B * 4901, B * 5001, and B * 4005, respectively. Serologic analysis definitively supports the essential role of leucine 145 within the B13-specific epitope. Furthermore, the involvement of glutamic 163 in the definition of both the specific B21 and polyspecific B15,B57 epitopes is suggested. B * 1303 constitutes a new example of how serology can give a distorted point of view of the structural relationship among alleles.