A noninvasive technology that indiscriminately detects tumor tissue in the brain could substantially enhance the management of primary or metastatic brain tumors. Although the documented molecular heterogeneity of diseases that initiate or eventually deposit in the brain may preclude identifying a single smoking-gun molecular biomarker, many classes of brain tumors are generally avid for transferrin. Therefore, we reasoned that applying a radiolabeled derivative of transferrin (⁸⁹Zr-labeled transferrin) may be an effective strategy to more thoroughly identify tumor tissue in the brain, regardless of the tumor’s genetic background. Transferrin was radiolabeled with ⁸⁹Zr, and its properties with respect to human models of glioblastoma multiforme were studied in vivo. In this report, we show proof of concept that ⁸⁹Zr-labeled transferrin (⁸⁹Zr-transferrin) localizes to genetically diverse models of glioblastoma multiforme in vivo. Moreover, we demonstrate that ⁸⁹Zr-transferrin can detect an orthotopic lesion with exceptional contrast. Finally, the tumor-to-brain contrast conferred by ⁸⁹Zr-transferrin vastly exceeded that observed with ¹⁸F-FDG, currently the most widely used radiotracer to assess tumor burden in the brain. The results from this study suggest that ⁸⁹Zr-transferrin could be a broadly applicable tool for identifying and monitoring tumors in the brain, with realistic potential for near-term clinical translation.