Differentiation of glioblastoma multiforme (GBM) and primary cerebral lymphoma (PCL) is important because the treatment strategies are substantially different. In patients with GBM, wide surgical resection followed by radiation therapy and chemotherapy with temozolomide is the choice of treatment, whereas patients with PCL usually need to receive high-dose methotrexate-based chemotherapy with or without radiation after stereotactic biopsy. Conventional MR imaging allows differentiation between these two entities because GBM usually exhibits a ring-shaped contrast-enhanced mass lesion with a hypointense central necrosis on contrast enhanced T1-weighted MR imaging, but PCL usually presents as a solid mass lesion with homogeneous contrast enhancement in immune-competent patients. However, in some cases atypical, solid enhancing GBM without visible necrosis may mimic PCL, and atypical PCL with visible necrosis may mimic GBM. Although some studies have shown statistically significant differences in apparent diffusion coefficient (ADC) values between the GBM and PCL,^1-4 others have reported that ADC might not be helpful due to substantial overlap in values for these two entities.^5,6 Further, it is noted that peritumoral edema plays an important role in differentiation of brain tumors.^7,8 The purpose of this study was to describe the MR imaging characteristics of GBMs and PCLs with emphasis on the difference of DWI signals and ADC values in tumoral necrosis, the most enhanced tumor area, and the peritumoral edema.This retrospective cohort study collected 124 patients in two years period, with 104 patients (58 men, 46 women, age range 8-87 years, median age 59 years) diagnosed with GBMs (WHO grade IV) by biopsy, and 20 immune-competent patients (8 men, 12 women, aged 38-77 years, mean age 62 years) with PCLs (diffuse large B cell lymphoma). All these patients had pretreatment MR (DWI/ADC) imaging. The MRI images were acquired using a 1.5T MR scanner. All of the patients underwent axial T1-weighted spin-echo (T1WI), T2-weighted imaging (T2WI) (fast spin-echo), fluid attenuated inversion recovery (FLAIR), T2*-weighted gradient-recalled echo (GRE), and post-contrast enhanced T1W images in axial and coronal sections with fat saturation. The DWI was performed by applying three sequential gradients in the x, y, and z directions with b =1000 sec/mm2. ADC maps were obtained from these imaging data. For DWI rating, each lesion was rated as predominantly hyperintense, isointense, or hypointense relative to the white matter. For ADC measurement, circular region of interest (ROI) with area range from 30 to 76mm² was placed within the necrotic area, the most enhanced area (tumor), and the peritumoral edema in all GBMs and PCLs (Figure 1). Receiver operating characteristic (ROC) analysis with optimal cut-off values and area-under-theROC curve (AUC) values were performed for each parameter to discriminate between GBM and PCL. For ratings of DWI signals, there was statistically significant difference (P<0.05) in the necrosis and peritumoral edema between these two different tumors. For ADC values, the median ADC values of GBMs were higher than PCLs in the necrosis and the most enhanced tumor, but lower than PCLs in the peritumoral edema (Figures 2). There was statistically significant difference (P<0.05) in the most enhanced tumor and the peritumoral edema between GBMs and PCLs. The optimal cutoff values of ADC for differentiating GBMs from PCLs were 1.85x10^-3 mm²/s in the necrosis, 0.765x10^-3 mm²/s in the most enhanced area, and 1.805x10^-3 mm²/s in the peritumoral edema (Figure 3). The discriminative ability of ADC values to differentiate these two entities, in decreasing order of AUC values, were ADC values in the most enhanced area (AUC, 0.76), the peritumoral edema (AUC, 0.75), and the necrosis (AUC, 0.65) (Figure 3).The results from this study showed that quantitative DWI parameters were able to show significant difference between GBMs and PCLs, with GBMs tended to have significantly higher ADC in the enhanced tumor area, and lower ADC in the peritumoral edema area than PCLs. It is postulated that lower ADC observed in PCLs may be due to higher degree of cellularity than GBMs. Whereas, GBMs tend to have peritumoral infiltration which leads to the lower ADC in the peritumoral edema area. Quantitative ADC values measured in these two areas thus can be used to improve diagnostic accuracy for these two brain tumor types. The histological underpinning of the ADC difference between these two tumors deserves further investigation.