Differentiating between brain abscesses and cystic brain tumors such as high-grade gliomas and metastases is often difficult with conventional MRI. The goal of this study was to evaluate the diagnostic utility of perfusion MRI to differentiate between these pathologies. MRI was performed in 19 patients with rim-enhancing brain lesions (4 pyogenic abscesses, 8 high-grade gliomas, 7 metastases). In addition to standard MR sequences, trace diffusion-weighted MRI with apparent diffusion coefficient (ADC) maps and perfusion-weighted MRI by using a first-pass gadopentetate dimeglumine T2*-weighted gradient echo single-shot echo-planar sequence were performed. Relative cerebral blood volume (rCBV) ratios were obtained via the values of the capsular portions of the lesions and the normal white matter. All the abscesses had markedly hyperintense signals in trace diffusion images, whereas they had significant hypointense signals in ADC images. In perfusion-weighted images, the capsular portions of the abscesses demonstrated low colored areas compared with the normal white matter and the rCBV ratio calculated was 0.76 ± 0.12 (mean ± SD). All but two of the cystic tumors showed low signal intensity on trace diffusion-weighted images and high signal intensity on ADC maps. Hyperintense signal was found in two brain tumors mimicking brain abscesses on trace diffusion images. The rCBV values in high-grade gliomas and metastases were 5.51 ± 2.08 and 4.58 ± 2.19, respectively. The difference between abscesses and cystic tumors was statistically significant (P = 0.003). Perfusion MRI may allow the differentiation of pyogenic brain abscess from cystic brain tumors, making it a strong additional imaging modality in the early diagnosis of these two entities.