It has been reported that high-resolution susceptibility-weighted imaging (HR-SWI) is a promising tool for assessing brain tumor characterization noninvasively. The purpose of this study was to determine the added value and diagnostic performance of HR-SWI for differentiating solitary enhancing brain lesions (SELs) by assessing intratumoral susceptibility signals (ITSSs). Sixty-four consecutive patients with SELs, without previous surgery, were retrospectively reviewed. We performed 2 consensus reviews, by using conventional MR images alone and with adjunctive HR-SWI. We applied an ITSS grading system based on the degree of the ITSS. Then, we compared the presence and grade of the ITSSs among specific pathologic types of SELs. Two observers diagnosed tumor pathology accurately in 43 (67%) of 64 SELs after reviewing the conventional images alone and 50 (78%) of 64 SELs after reviewing the adjunctive HR-SWI (P = .016, McNemar test). ITSSs were seen in 25 (100%) of 25 glioblastoma multiformes (GBMs), in 2 (40%) of 5 anaplastic astrocytomas, and in 11 (73%) of 15 metastatic tumors. Although the ITSSs were unable to distinguish between GBMs and solitary metastatic tumors, differentiation between GBMs and solitary metastatic tumors was achieved (P = .01) by using a high ITSS degree (grade 3). Moreover, the ITSSs could discriminate high-grade gliomas from lymphomas and nontumorous lesions with a specificity of 100% (P < .0001). The use of ITSSs on HR-SWIs significantly improves the accuracy for the differential diagnosis of SELs compared with the use of conventional MR imaging alone.