Secondary amyloid A (AA) amyloidosis is an important complication of rheumatoid arthritis (RA) and has remarkable variation in frequency worldwide. It is a serious, potentially life-threatening disorder caused by deposition in organs of AA fibrils, which are derived from the circulatory, acute-phase-reactant, serum amyloid A protein (SAA). The SAA1.3 allele can serve not only as a risk factor for the association of AA amyloidosis but also as a poor prognostic factor in Japanese RA patients. Both the association of AA amyloidosis arising early in RA disease course and symptomatic variety and severity were found in amyloidotic patients carrying the SAA1.3 allele. Etanercept for patients with AA amyloidosis who carry the SAA1.3 allele showed the amelioration of rheumatoid inflammation, including marked reduction of SAA and improvement of renal function. In light of the SAA1.3 allele significance in Japanese RA patients, both a tight control by disease-modifying antirheumatic drugs and an early intervention of biologics for RA inflammation should be applied to suppress acute-phase response, thus preventing the association of AA amyloidosis. It is suggested that SAA plays not only an important role in the development of AA amyloidosis but also interacts with events closely involved in metabolic syndrome as a high- and low-grade inflammatory modulator, respectively.