Nuclear imaging offers a potential noninvasive means of determining the histology of renal tumors. The aim of this study was to evaluate the accuracy of technetium-99m (99mTc)–sestamibi single-photon emission computed tomography/x-ray computed tomography (SPECT/CT) for the differentiation of oncocytomas and hybrid oncocytic/chromophobe tumors (HOCTs) from other renal tumor histologies. In total, 50 patients with a solid clinical T1 renal mass were imaged with 99mTc-sestamibi SPECT/CT prior to surgical resection. Preoperative SPECT/CT scans were reviewed by two blinded readers, and their results were compared with centrally reviewed surgical pathology data. Following surgery, 6 (12%) tumors were classified as renal oncocytomas and 2 (4%) as HOCTs. With the exception of 1 (2%) angiomyolipoma, all other tumors were renal cell carcinomas (82%). 99mTc-sestamibi SPECT/CT correctly identified 5 of 6 (83.3%) oncocytomas and 2 of 2 (100%) HOCTs, resulting in an overall sensitivity of 87.5% (95% confidence interval [CI], 47.4−99.7%). Only two tumors were falsely positive on SPECT/CT, resulting in a specificity of 95.2% (95% CI, 83.8−99.4%). In summary, 99mTc-sestamibi SPECT/CT is a promising imaging test for the noninvasive diagnosis of renal oncocytomas and HOCTs. Patient summaryWe found that the imaging test 99mTc-sestamibi SPECT/CT can be used to accurately diagnose two types of benign kidney tumors. This test may be eventually used to help better evaluate patients diagnosed with a renal tumor.