Rheumatoid arthritis (RA) is currently believed to have originated in America, and after the discovery of this continent in 1492, to have been exported to the Old World. We evaluated the genetic predisposition to RA in the "Braids Lady" from Arezzo (Italy), a partially mummified woman's body dating back to the end of 1500 AD which presents the anatomical and pathological features of this disease. The study of the polymorphic HLA-DRB1 locus, which includes alleles strongly associated with RA onset, has received much attention over recent years, especially the loci codifying for the DR1 and DR4 antigens, widely represented in the Mediterranean population, and for DR14, widespread among Native Americans. Molecular analysis was performed on extracts of DNA from the mummy, firstly from histological bone sections and then from the whole bone. Two different HLA typing techniques, PCR-sequence-specific oligonucleotides (PCR-SSO) and PCR-sequence-specific primers (PCR-SSP), were employed to identify HLA-DRB alleles. Both genotyping methods showed that the "Braids Lady" carried the DRB1*0101 allele, the serological equivalent of the DR1 antigen. Although the possession of RA risk factor genes cannot be considered a diagnostic marker, the positive result of the Italian mummy for DRB1*0101 and the RA features present, support the idea that this pathology was present in the Old World from at least the mid-16th century. A pathogenetic hypothesis of RA which might well explain its worldwide diffusion is the "molecular mimicry", resulting from a cross-reactive antibody response between certain microbial antigens and shared epitopes of specific HLA-DR1, DR4 and DR14 susceptibility alleles, the frequency of which varies among different ethnic groups.