Anti-
RNA Polymerase III antibodies are the most frequent anti-nuclear
antibodies in
systemic sclerosis, after anti-centromere and anti-
Topoisomerase I. Considering their specificity for
systemic sclerosis, they have been included in 2013 American College of Rheumatology/European League Against
Rheumatism classification criteria for
systemic sclerosis. They were first identified in 1993 using an immunoprecipitation method; the subsequent diffusion of commercial assays, based on the
enzyme-linked
immunosorbent assay or multiplex line immunoblot techniques, has allowed an increasing number of
systemic sclerosis patients to be tested for this
autoantibody; nevertheless, the diffusion of this test in
systemic sclerosis patients is probably still sub-optimal. Anti-
RNA Polymerase III antibodies have been associated with important clinical manifestations: rapid and diffuse cutaneous involvement, joint
contractures, scleroderma renal crisis,
gastric antral vascular ectasia and
malignancies synchronous to
systemic sclerosis onset. Moreover, other possible clinical associations, including
pulmonary hypertension, still need confirmation. Since the correct approach for screening for anti-
RNA Polymerase III antibodies in patients with suspected or definite
systemic sclerosis is still debated, possible strategies are proposed here. Moreover, issues that are still controversial are discussed, including the interpretation of multiple simultaneous positivity for anti-
RNA Polymerase III antibodies and other
autoantibodies in line immunoassay, and the possible relevance of anti-
RNA Polymerase III antibodies titre.