An exploratory mass cytometry analysis identified candidate markers for distinguishing between patients with newly-diagnosed rheumatoid arthritis (RA) and healthy individuals. A panel of 13 phenotyping and 10 functional markers were used to characterize TNF-mediated signalling patterns in peripheral blood mononuclear cells from patients with RA or healthy individuals, leading to the identification of a small set of RA-specific markers. A combined model of these markers could correctly classify 18 out of 20 patients with RA and 17 out of 20 healthy individuals. These markers could potentially be used for the diagnosis and stratification of RA in the future.