ACKR1, located on chromosome 1q23. 2, is the gene that encodes a glycoprotein expressing the Duffy blood group antigens. This gene is transcribed in two mRNA variants yielding two isoforms, encoding proteins with 338 and 336 amino acids. This review provides a general overview of the Duffy blood group to characterise and elucidate the genetic basis of this system. The Fy a and Fy b antigens are encoded by co-dominant FY* A (FY* 01) and FY* B (FY* 02) alleles, which differ by c. 125G> A (rs12075), defining the Fy (a+ b−), Fy (a− b+) and Fy (a+ b+) phenotypes. The Fy (a− b−) phenotype that occurs in Africans provides an explanation for the apparent absence of Plasmodium vivax in this region: this phenotype arises from homozygosity for the FY* B allele carrying a point mutation c. 1-67T> C (rs2814778), which prevents Fy b antigen expression only in red blood cells. The same mutation has also been found on the FY* A allele, but it is very rare. The Fy (a− b−) phenotype in Europeans and Asians arises from mutations in the coding region of the FY* A or FY* B allele, preventing Duffy antigen expression on any cell in the body and thus are true Duffy null phenotypes. According to the International Society for Blood Transfusion, ten alleles are associated with the null expression of the Fy antigens. Furthermore, different allelic forms of FY* B modify Fy b antigen expression, which may result in very weak or equivocal serology results. The mostly common found variants, c. 265C> T (rs34599082) and c. 298G> A (rs13962)-previously defined in combination only with the FY* B allele-have already been observed in the FY* A allele. Thus, six alleles have been recognised and associated with weak expression of the Fy antigens. Considering the importance of the Duffy blood group system in clinical medicine, additional studies via molecular biology approaches must be performed to resolve and clarify the discrepant results that are present in the erythrocyte phenotyping.