Tc-99m MIBI is a small lipophilic radioligand that enters cells by diffusion and is preferentially trapped in mitochondria. As a result of the high mitochondrial activity in tumors, Tc-99m MIBI accumulates significantly more in tumor tissue compared with normal tissues. Accordingly, Tc-99m MIBI has been used successfully to visualize primary, metastatic, and recurrent tumor. In brain tumors, Tc-99m MIBI SPECT has been shown to identify tumor recurrence after treatment in high-grade gliomas. In this report, early (30 minutes after injection) and delayed (4 hours after injection) Tc-99m MIBI SPECT did not visualize a histopathologically proved recurrent high-grade oligodendroglioma. Increased vascular supply, disruption of the blood-brain barrier, high-grade cancer, and viability of tumor cells are decisive factors related to increased Tc-99m MIBI uptake in brain tumors. However, the authors' results suggest that still other mechanisms may be involved in Tc-99m MIBI accumulation, which may account for false-negative imaging in brain tumors.