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Aberrant expression of microRNAs (miRNAs) contributes to the progression and outcomes of several types of tumor, while circulating miRNAs have been reported to act as biomarkers for several types of cancer. To identify specific circulating miRNAs associated with multiple myeloma (MM), a miRNA microarray analysis was used, which identified 8 upregulated miRNAs and 4 downregulated miRNAs in the plasma of 6 patients with MM compared with 6 healthy individuals. Based on the microarray results, the 8 miRNAs (miR-125b-5p, miR-483-3p, miR-4326, miR-6894-3p, miR-4498, miR-490-3p, miR-7155-5p and miR-937-3p), which were notably upregulated in MM patients were chosen for a second clinical study in 20 healthy controls and 35 patients with MM using reverse transcription- quantitative polymerase chain reaction. Receiver operating characteristic analysis demonstrated that miR-125b-5p and miR-490-3p displayed considerable diagnostic accuracy for MM with areas under the curve of 0.954 (P<0.001) and 0.866 (P=0.028), respectively. In addition, the plasma level of miR-125b-5p was associated with the international staging system disease stage. Patients with higher levels of plasma miR-125b-5p had a significantly shorter event-free survival. However, miR-490-3p levels were not associated with event-free survival (P>0.05). In summary, miR-125b-5p may serve as a potential clinical biomarker for MM.