The aim of this study is to evaluate the diagnostic efficiency of magnetic resonance imaging (MRI) of single parameters, unimodality, and bimodality in distinguishing glioblastoma (GBM) from atypical primary central nervous system lymphoma (PCNSL) based on diffusion-weighted imaging (DWI), dynamic susceptibility contrast (DSC) enhancement, diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (1H-MRS) findings.The cohort included 108 patients pathologically diagnosed with GBM and 54 patients pathologically diagnosed with PCNSL. Pretreatment morphological MRI, DWI, DSC, DTI and MRS were all performed on each patient. The quantitative parameters of multimodal MRI were measured and compared between the patients in the GBM and atypical PCNSL groups, and those parameters showing a significant difference (p < 0.05) between patients in the GBM and atypical PCNSL groups were used to develop one-parameters, unimodality, and bimodality models. We evaluated the efficiency of different models in distinguishing GBM from atypical PCNSL by performing receiver operating characteristic analysis (ROC).Atypical PCNSL had lower minimum apparent diffusion coefficient (ADCmin), mean ADC (ADCmean), relative ADC (rADC), mean relative cerebral blood volume (rCBVmean), maximum rCBV (rCBVmax), fractional anisotropy (FA), axial diffusion coefficient (DA) and radial diffusion coefficient (DR) values and higher choline/creatine (Cho/Cr) and lipid/creatine (Lip/Cr) ratios than GBM (all p < 0.05). The rCBVmax, DTI and DSC + DTI data were optimal models of single-parameter, unimodality and bimodality for differentiation of GBM from atypical PCNSL, yielding areas under the curves (AUCs) of 0.905, 0.954, and 0.992, respectively.Models of single-parameter, unimodality and bimodality based on muti multiparameter functional MRI may help to discriminate GBM from atypical PCNSL.© 2023 The Authors.