To determine retrospectively whether unenhanced computed tomographic (CT) images of the brain have added value in distinguishing tumefactive demyelinating lesions (TDLs) from primary glioma or central nervous system (CNS) lymphoma, compared with conventional contrast material-enhanced magnetic resonance (MR) images only. This study was approved by the institutional review board, and informed consent was waived. Unenhanced CT and MR images in 15 patients with TDLs (seven women, eight men; mean age, 42 years; range, 27-57 years) and 48 patients with primary brain tumor (27 women, 21 men; mean age, 48 years; range, 19-70 years; 10 lymphomas, 38 gliomas) were retrospectively reviewed. The CT attenuation of regions that were enhanced or unenhanced at MR imaging was visually categorized into three grades, and CT attenuation values were determined quantitatively. The diagnostic accuracy of MR imaging for differentiating TDLs from tumors was compared with that of MR imaging plus CT. The following MR imaging features were found more frequently in patients with TDL than in those with brain tumor: incomplete rim enhancement, mixed T2-weighted iso- and hyperintensity of enhanced regions, absence of a mass effect, and absence of cortical involvement (all P values < .05). CT hypoattenuation of MR enhanced regions was observed in 14 (93%) of 15 patients with TDL but in only two (4%) of 48 patients with tumor. The CT attenuation of MR enhanced regions was significantly lower for patients with TDL than for those with tumor (P < .001). The diagnostic accuracy of CT plus MR imaging was significantly higher than that of MR imaging alone (97% vs 73.0%, respectively; P < .001), and the diagnostic accuracy of CT was significantly higher than that of unenhanced T1-weighted MR imaging (95% vs 63%, P < .001). Unenhanced CT plus MR imaging was more accurate for distinguishing TDLs from glioma or CNS lymphoma than contrast-enhanced MR imaging alone.