Seventy-two novel human leukocyte antigen (HLA) class I and class II alleles are described from volunteers for the 'Be The Match Registry®': 17 HLA-A alleles, 12 HLA-C alleles, 31 HLA-B alleles and 12 HLA-DRB1 alleles. Forty-six (≈ 64%) of the 72 novel alleles are single-nucleotide substitution variants when compared with their most homologous allele. Five of these single-nucleotide variants are silent substitutions and one creates a non-expressed allele (B*44:108N). The remaining novel alleles differ from their most similar allele by two to five nucleotide substitutions. One of the novel HLA-C alleles (C*07:150Q) is of questionable expression due to an insertion of 21 nucleotides starting at codon 143 that adds seven amino acids to exon 3. An inter-locus gene conversion may have created the novel allele HLA-A*23:31 that shares its codon differences with HLA-B*07:28. Some of the new alleles encode novel codons and unique amino acid changes at polymorphic positions in the HLA-A (codons 116 and 150), HLA-C (codon 114), HLA-B (codons 11, 21, 35, 42, 48, 73, 98 and 170) and HLA-DRB1 (codon 29) loci.