Purpose With conventional MRI, it is often difficult to effectively differentiate between contrast-enhancing brain tumors, including primary central nervous system lymphoma (PCNSL), high-grade glioma (HGG), and metastasis. This study aimed to assess the discrimination ability of the parameters obtained from DWI and the percentage signal recovery- (PSR-) optimized protocol of DSC-MRI between these three tumor types at an initial step. Methods DSC-MRI using a PSR-optimized protocol (TR/TE = 1500/30 ms, flip angle = 90 degrees, no preload) and DWI of 99 solitary enhancing tumors (60 HGGs, 24 metastases, 15 PCNSLs) were retrospectively assessed before treatment. rCBV, PSR, ADC in the tumor core and rCBV, and ADC in peritumoral edema were measured. The differences were evaluated using one-way ANOVA, and the diagnostic performance was evaluated using ROC curve analysis. Results PSR in the tumor core showed the best discriminating performance in differentiating these three tumor types with AUC values of 0.979 for PCNSL vs. others and 0.947 for HGG vs. metastasis. The ADC was only helpful in the tumor core and distinguishing PCNSLs from others (AUC = 0.897). Conclusion Different from CBV-optimized protocols (preload, intermediate FA), PSR derived from the PSR-optimized protocol seems to be the most important parameter in the differentiation of HGGs, metastases, and PCNSLs at initial diagnosis. This property makes PSR remarkable and carries the need for comprehensive DSC-MRI protocols, which provides PSR sensitivity and CBV accuracy together, such as the preload use of the PSR-optimized protocol before the CBV-optimized protocol.