Purpose of Review: The majority of enhancing renal masses cannot be characterized through imaging as malignant or benign; however, such characterization could save patients from unnecessary surgery and/or biopsy and associated morbidity. Herein, we review the recent literature on the emerging use of 99mTc-MIBI SPECT/CT in preoperative differentiation of enhancing renal masses. Recent Findings: Recent reports have shown that 99mTc-MIBI SPECT/CT imaging can differentiate mitochondrial-rich, benign, or indolent renal masses from renal cell carcinoma. These studies demonstrate good correlation between a positive 99mTc-MIBI SPECT/CT scan and a pathologically proven diagnosis of renal oncocytoma and hybrid oncocytic/chromophobe tumor. In addition, there is excellent correlation between a negative scan and a diagnosis of clear cell subtype of renal cell carcinoma. Summary: Preoperative 99mTc-MIBI SPECT/CT offers a non-invasive method for differentiating renal lesions with low aggressiveness from other RCCs, in particular, clear cell renal cell carcinoma.