BACKGROUND: The management of multiple myeloma is challenging because the disease is incurable and unexpected relapses can threaten a patient's survival. Several assessment systems are currently available, but they often require invasive or costly procedures (e.g., instrumental bone marrow and whole-body examinations) or rely on non-specific markers in blood and urine that may not be sufficient to assess and monitor the disease. AIMS: To address some of these limitations, the aim of this study was to evaluate the potential use of soluble B-Cell Maturation Antigen (BCMA), a promising new serum biomarker, as a toll for moniting multiple myeloma patients. MATERIALS & METHODS: An unselected cohort of 57 newly diagnosed or relapsed myeloma patients was followed up for 6 months after starting a new therapy. Soluble BCMA levels were measured in peripheral blood using a simple and inexpensive ELISA assay. RESULTS: Soluble BCMA was detectable in peripheral blood by a simple and inexpensive assay in all patients, even in non-secretory disease or during BCMA-targeted therapies, and significant changes in its levels were observed over time. The analysis showed that the decrease in sBCMA at 1 and 6 months reflects the quality of the clinical response to anti-myeloma regimens. DISCUSSION & CONCLUSION: The data provide interesting insights into the usefulness of sBCMA as a non-invasive tool for early assessment of treatment efficacy. Its simple and cost-effective detection in peripheral blood could provide clinicians with an addiotional resource for monitoring disease progression and tailoring treatment strategies.