Amyloid A (AA) amyloidosis secondary to rheumatoid arthritis (RA) is an uncommon yet important complication. There is both startling variation and different prevalence among different races in the frequency of AA amyloidosis worldwide and the fact that AA amyloidosis is not consistently related to length and severity of RA inflammation suggests the involvement of genetic factors. Serum amyloid A (SAA)1.3 allele, in particular homozygosity of this allele, has been revealed to be not only a risk factor for the association of AA amyloidosis but also a poor prognostic factor in survival of Japanese patients with RA. This leads us to the notion of clinical significance of SAA1.3 allele in the management of Japanese RA patients. Renal involvement is a pivotal clinical manifestation in the development of AA amyloidosis. Cyclophosphamide is superior to methotrexate in the medication of RA patients with AA amyloidosis. Etanercept showed an efficacy for patients with AA amyloidosis secondary to RA who carry SAA1.3 allele, suggesting a possibility of the drug as a tailor-made medicine. It is probable that SAA plays not only an important role in the development of AA amyloidosis but also interacts as a factor closely involved in metabolic syndrome in health and disease.