The study aims to comprehensively assess the profiles of myositis-specific autoantibodies (MSAs) in Chinese patients with polymyositis (PM)/dermatomyositis (DM) and compare them with a Japanese cohort. One hundred forty-five Chinese patients (68 classic DM, 25 clinically amyopathic DM [CADM], and 52 PM) and 165 Japanese patients (56 classic DM, 52 CADM, and 57 PM) were recruited. MSAs were measured with immunoprecipitation, enzyme-linked immunosorbent assay, or immunoprecipitation-immunoblotting. MSA frequencies were compared. The overall frequency of anti-melanoma differentiation-associated gene 5 (MDA5) antibodies was significantly higher in the Chinese patients than in the Japanese cohort (36.6 % [53/145] versus 15.8 % [26/165], respectively, P < 0.001), whereas the frequencies of anti-signal recognition particle (SRP) antibodies (1.4 % [2/145] versus 7.9 % [13/165], respectively, P = 0.008) and anti-aminoacyl-transfer RNA synthetase (anti-ARS) antibodies (27.6 % [40/145] versus 40 % [66/165], respectively, P = 0.02,) were significantly lower. The significantly lower frequency of anti-ARS antibodies and significantly higher frequency of anti-MDA5 antibodies in the Chinese patients were observed in the classic DM subset (14.7 % [10/68] versus 46.4 % [26/56], respectively, P < 0.001, and 45.6 % [31/68] versus 5.4 % [3/56], respectively, P < 0.001) and CADM subset (8.0 % [2/25] versus 28.8 % [15/52], respectively, P = 0.04, and 88.0 % [22/25] versus 44.2 % [23/52], respectively, P = 0.0002), but not in the PM subset. The first detailed profile of MSAs in Chinese patients with PM/DM was established. The differences in MSA frequencies in the Chinese cohort and Japanese cohort suggest underlying genetic and/or environmental differences between these two populations. Key Messages • A significantly higher frequency of anti-melanoma differentiation-associated gene 5 (MDA5) antibodies was observed in Chinese patients with polymyositis/dermatomyositis (PM/DM) than in Japanese patients. • Our findings suggest that distinct genetic and/or local environmental factors affect Chinese and Japanese patients with PM/DM, who have been considered a "homogeneous" population in previous studies.