Objective. Bone marrow stromal cell antigen 1 (BST‐1) is a novel glycosyl phosphatidylinositol–anchored ectoenzyme, which is overexpressed on bone marrow stromal and synovial cell lines derived from patients with rheumatoid arthritis (RA). To investigate the pathophysiologic roles of BST‐1 in RA, we established an enzyme‐linked immunosorbent assay (ELISA) system to detect the soluble form of BST‐1 (sBST‐1) and examined levels of sBST‐1 in the sera of RA patients. Methods. Concentrations of sBST‐1 in sera from healthy donors and from patients with RA, osteoarthritis, Sjögren's syndrome, and systemic lupus erythematosus were measured with the ELISA. Results. In 7% of the RA patient samples (10 of 143), concentrations of serum sBST‐1 were higher (∼30–50‐fold) than in non‐RA samples. Serum sBST‐1 concentrations showed no correlation with age, C‐reactive protein level, or rheumatoid factor level. All RA patients with high concentrations of serum sBST‐1 had severe disease with involvement of several large joints. Conclusion. We believe the measurement of serum sBST‐1 may have prognostic value, but further analysis is necessary to clarify the clinical significance of elevated sBST‐1 in RA.