We describe here a novel HLA-DRB1* allele, DRB1*0331, observed from a Taiwanese bone marrow donor using DNA sequence-based typing (SBT) method. The 'new' allele differs from DRB1*0306 and DRB1*0325 by one nucleotide at positions 196 and 227, respectively. Nucleotide mutations caused amino acid substitutions from N to Y at codon 37 and from F to Y at codon 47, as compared with amino acid sequence encoded by the DRB1*030101 allele. The donor was first typed as DRB1*0403/0406/0439/0441/0446/0451/0452 (NMDP code DRB1*04XX) and DRB1*0304/0323/0325 (NMDP code DRB1*03APDA) by sequence-specific oligonucleotide (SSO) typing kit. Subsequent typing of the donor by high-resolution sequence-specific primer (SSP) protocol indicated DRB1*0403 and DRB1*0306. The anomalous result of DRB1*03 was resolved by SBT and recognized as DRB1*0331. We concluded that SSP or SSO alone may mistype a precedent unrecognized allele and that two different typing techniques or SBT may have to be employed to safe guard true HLA typing when rare alleles are encountered at the first time.