Magnetic Resonance Diffusion-Weighted Imaging (DWI) has been reported to be helpful for the differential diagnosis between abscesses and cystic/necrotic brain tumors. However the number of patients is still limited, and the sensitivity and specificity of the method remain to be confirmed. The primary purpose of this study was to investigate a larger sample of patients, all investigated under the same experimental conditions, in order to obtain statistically significant data. Moreover, there is no consensus about the appropriate values of b required to use to make an accurate diagnosis from DWI. The secondary purpose of this study was to determine the discriminating threshold b values for raw diffusion-weighted images and for normalized diffusion-weighted images. On the basis of 14 abscesses, 10 high-grade gliomas and 2 metastases, we show that the calculation of accurate Apparent Diffusion Coefficient (ADC) values gives a specificity rate of 100%. Without ADC calculation, we show that image normalization is required to make an accurate differential diagnosis, and we highlight the ability of DWI to discriminate between brain abscesses and cystic/necrotic brain tumors using normalized signal intensity at lower b values (503 s/mm(2)) than usual.