Systemic sclerosis (SSc) is a connective tissue disorder characterized by microvascular damage and excessive fibrosis of the skin and internal organs with autoimmune background. One representative feature of the immunological abnormalities in SSc patients is the presence of antinuclear antibodies (ANA). More than 90% of patients with SSc are positive for ANA. Although a role of ANA in the pathogenesis in SSc remains unclear, the particular ANA are often indicative of clinical feature, disease course, and overall severity. Therefore, subgrouping patients based on the type of autoantibodies present can be useful in diagnosis and management. Anticentromere antibody (ACA), anti-DNA topoisomerase I antibody (Ab), and anti-RNA polymerase Ab are the representative autoAbs found in patients with SSc. Other serum ANA found in SSc include anti-Th/To Ab, anti-U3RNP Ab, anit-human upstream-binding protein (hUBF) Ab, anti-centriole Ab, anti-U1RNP Ab, anti-Ku Ab, and anti-PM-Scl Ab. It is documented that the prevalence of SSc-related Abs and clinical characteristics of patients with SSc are influenced by ethnicity. Identifying several SSc-related Abs requires a complicated technique that include immunoprecipitation assay. Establishment of a system routinely available to screen ANA specificities such as enzyme-linked immunosorbent assay is needed.