Distinguishing neoplastic from nonneoplastic intracerebral hematoma has great clinical relevance for the appropriate management of patients. Imaging is not always able to clearly identify a tumor-related intraparenchymal cerebral hemorrhage (ICH), especially in the acute phase, the diagnosis being frequently based on evolution patterns. The aim of this study was to test the value of (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) SPECT as a noninvasive diagnostic tool in early diagnosis of hemorrhagic brain neoplasm. METHODS We prospectively studied 29 patients harboring a nontraumatic acute onset of clinical deterioration caused by ICH with atypical clinical or neuroradiologic features. All patients underwent (99m)Tc-MIBI SPECT within 48 h from the clinical onset. Early and delayed images were obtained. Both visual and semiquantitative analyses were performed. The (99m)Tc-MIBI index was obtained from both early and delayed images and the retention index was calculated. RESULTS In 19 patients (65.5%), a nonneoplastic hemorrhage (15 vascular degenerative diseases, 2 cavernous angiomas, 1 thrombosed middle cerebral artery giant aneurysm, and 1 sinus rectus thrombosis) was diagnosed by clinical and neuroradiologic follow-up or open surgery. In 10 patients (34.5%), a neoplastic hemorrhage (6 metastases, 2 glioblastomas multiforme, 1 ependymoma, and 1 intracranial angioblastic meningioma) was diagnosed by direct histologic typing (open surgery or stereotactic biopsy). In all neoplasm-related hemorrhages, a focal increased tracer uptake was observed in the area of the lesion, whereas no focal increased tracer uptake was noted in all nonneoplastic hematomas. A wide cutoff in the early ratio between neoplastic and nonneoplastic hemorrhages was found. Moreover, a statistically significant difference was found in the delayed ratio (P < 0.01) and the retention index (P < 0.05) between the 2 groups. CONCLUSIONS Our data suggest that (99m)Tc-MIBI SPECT could play a role in the early noninvasive diagnostic work-up of hemorrhagic brain lesions, allowing a clear differentiation between neoplastic and nonneoplastic ICHs. The high availability and low cost of this nuclear medicine technique can be considered additional advantages.