<h4>Objective</h4>To delineate the clinical characteristics, identify risk factors (including the exploratory role of anti-Ro-52 antibody), and assess the prognostic implications of malignancy in patients with anti-synthetase syndrome (ASyS).<h4>Methods</h4>In this retrospective multicenter study, patients with idiopathic inflammatory myopathies (IIM) were analyzed, comprising 103 ASyS and 261 non-ASyS patients [including dermatomyositis (<i>n</i> = 195), immune-mediated necrotizing myopathy (<i>n</i> = 9), overlap myositis (<i>n</i> = 12), and other IIM subtypes (<i>n</i> = 45)]. This evidence concerns the gene TRIM21 and acquired idiopathic inflammatory myopathy.