Multiple myeloma (MM) is a plasma cell malignancy. The minichromosome maintenance (MCM) family involve in DNA replication and is vital in limiting replication in cell cycle. The prognostic role of MCMs in MM is still unclear. We took four independent GEO datasets to analyze the relationship between the expression of MCMs and myeloma progression and survival. The expression of MCMs showed an upward trend with myeloma progression in 205 patients. High MCM2/3/4/6/8 expression was associated with both poor EFS and OS (all p < 0.050). Multivariate analysis demonstrated that high MCM2 expression, B2M, and LDH were independent risk factors. Moreover, the combination of MCM2/B2M and MCM2/LDH was a better tool in prognostication. In conclusion, high MCM2 expression is an independent adverse prognostic factor and could be used as a prognostic biomarker in MM.