Interferon signature is one of the key pathogenic pathways in idiopathic inflammatory myopathies (IIMs), particularly in dermatomyositis (DM). The aim of this study was to analyze Siglec-1, an interferon-inducible receptor, on different monocyte subsets in IIM subtypes and investigate its association with disease activity measures. Siglec-1 expression was measured by 8-color flow cytometry in 62 IIM patients and 10 healthy controls (HC). Disease activity was assessed using the International Myositis Assessment and Clinical Studies (IMACS) core set measures. Active DM patients exhibited significantly higher Siglec-1 mean fluorescence intensity (MFI) compared to inactive subgroups and HCs in every monocyte subset. Intermediate monocytes displayed the highest Siglec-1 expression across all groups and the strongest associations between disease activity markers. Siglec-1 expression on monocyte subsets was strongly associated with global, extramuscular global, constitutional, cutaneous, muscular, and gastrointestinal activity measures, but not with pulmonary, skeletal, and cardiac activities in the DM population. The best indicator of DM global disease activity among the examined biomarkers was Siglec-1 MFI on intermediate monocytes. Siglec-1 on intermediate monocytes correlates strongly with organ-specific clinical and biochemical markers of disease activity; therefore, it is a candidate biomarker for monitoring IIM disease activity. Siglec-1 could be useful in patient selection for interferon-targeted treatments.