Steady Reynolds-averaged Navier-Stokes (RANS) simulation with the mixing-plane approach is the most common procedure to obtain the performance of a centrifugal compressor in an industrial development process. However, the accurate prediction of complicated flow fields in centrifugal compressors is the most significant challenge. Some phenomena such as the impeller-diffuser flow interaction generates the unsteadiness which can affect the steady assumption. The goal of this study is to investigate the differences between the RANS and URANS simulation results in a centrifugal compressor stage. Simulations are performed at three operating points: near surge (NS), design point (DP), and near choke (NC). The results show that the RANS simulation can predict the overall performance with reasonable accuracy. However, the differences between the RANS and URANS simulation are quite significant especially in the region that the flows are highly unsteady or nearly separated. The RANS simulation is still not very accurate to predict the time-dependent quantities of the flow structure. It shows that the URANS calculations are necessary to predict the detailed flow structures and performance. The phenomena and mechanisms of the complex and highly unsteady flow in the centrifugal compressor with a vaned diffuser are presented and analyzed in detail.