Background: Multiple myeloma (MM) with 1q21 gains invariably has a poor prognosis. Many recent studies have reported the relationship between micro (mi)RNA expression and MM prognosis. However, there is little information on the association between miRNA alterations and 1q21 gains. Methods: We compared the miRNA expression profiles of MM with 1q21 gains and MM with normal fluorescence in situ hybridisation (FISH) by gene expression array. Differentially expressed miRNAs were identified using Affymetrix TAC software. Thresholds were defined as a false discovery rate <0.05, p value <0.05, and n-fold change >2. Results: Six miRNAs (let-7f-5p and -7g-5p, and miR-29a-3p, -29b-1-5p, -331-3p, and -223-3p) were downregulated and 4 (miR-30e-5p, -17-3p, -18b-5p, and -19a-3p) were upregulated in MM with 1q21 gains relative to MM with normal FISH. Conclusions: The identified set of miRNAs can serve as biomarkers for distinguishing MM with 1q21 gains from MM with normal FISH.