We present four cases of primary brain tumors in which both Tc-99m HMPAO and Tl-201 chloride localized in the tumors, but with discordant distribution. Larger accumulation with Tc-99m HMPAO than Tl-201 chloride was observed in two patients (one astrocytoma and one meningioma). This was related to localization of the tracer in the tumor as well as in the adjacent hyperemic region as compared with the MRI findings. In one patient with pituitary adenoma, Tc-99m HMPAO localized in nearly the entire tumor, similar to the result with Tl-201 chloride. In one patient with astrocytoma, Tc-99m HMPAO showed partial tumor accumulation, less than that shown by Tl-201 chloride. Tc-99m HMPAO uptake by brain tumors does not always reflect the viable tumor burden as compared with the distribution of Tl-201 chloride and MRI or CT findings.