Background: One type of malignant plasma cell disease is multiple myeloma (MM). MiR-331-3p contains the potential binding sites of LncRNA human urothelial carcinoma associated 1 (UCA1). The purpose of this study was to assess the significance of serum lncRNA UCA1 to MM diagnosis in relation to miRNA-331-3p. Methods: This study type was a case-control observational design. Serum from 53 patients with MM who were recently diagnosed and 53 age- and sex- matched healthy controls was collected. The expressions of lncRNA UCA1 and miRNA 331-3p were detected by real-time qPCR. Results: The lncRNA UCA-1 was highly expressed in MM patients, and miRNA 331-3p was down-expressed. Serum lncRNA UCA-1 levels were significantly increased with ISS stages. However, lncRNA UCA-1 expression levels did not differ with Durie-Salmon stages, renal dysfunction, and bone damage. On the other hand, miRNA 331-3p expression levels were significantly reduced with Durie-Salmon stages and bone damage. The lncRNA UCA-1 expression showed a sensitivity and specificity of 88.7% and 100%. The miRNA 331-3p expression showed a sensitivity and specificity of 83% and 100%. Multivariate analysis showed that lncRNA UCA1 (p=0.016) and miRNA 331-3p (p=0.008) were independent predictors for MM diagnosis. Conclusions: High expression of lncRNA UCA1 was detected in myeloma patients, which increased significantly with ISS. The miRNA331-3p was downregulated in MM. Both markers seem to be predictors for MM diagnosis, but the lncRNA UCA1 showed higher sensitivity and specificity. The lncRNA UCA1 and miRNA 331-3p were independent predictors for MM diagnosis.