In 1990, 90 years after the discovery of ABO blood groups by Karl Landsteiner, my research team at the Molecular Biology Laboratory of the now-defunct Biomembrane Institute elucidated the molecular genetic basis of the ABO polymorphism. Henrik Clausen, Head of the Immunology Laboratory, initiated the project by isolating human group A transferase (AT), whose partial amino acid sequence was key to ... [Show full abstract] its success. Sen-itiroh Hakomori, the Scientific Director, provided all the institutional support. The characterization started from the 3 major alleles (A1, B, and O), and proceeded to the alleles of A2, A3, Ax and B3 subgroups and also to the cis-AB and B(A) alleles, which specify the expression of A and B antigens by single alleles. In addition to the identification of allele-specific single nucleotide polymorphism (SNP) variations, we also experimentally demonstrated their functional significance in glycosyltransferase activity and sugar specificity of the encoded proteins. Other scientists interested in blood group genes later characterized more than 250 ABO alleles. However, recent developments in next-generation sequencing have enabled the sequencing of millions of human genomes, transitioning from the era of genetics to the era of genomics. As a result, numerous SNP variations have been identified in the coding and noncoding regions of the ABO gene, making ABO one of the most studied loci for human polymorphism. As a tribute to Dr. Hakomori's scientific legacy, a historical overview in molecular genetic/genomic studies of the human ABO gene polymorphism is presented, with an emphasis on early discoveries made at his institute.