The increasing evidence of oncocytic renal tumors positive in Tc Sestamibi Single Photon Emission Tomography/Computed Tomography (SPECT/CT) examination calls for the development of diagnostic tools to differentiate these tumors from more aggressive forms. This study combined radiomics analysis with the uptake of Tc Sestamibi on SPECT/CT to differentiate benign renal oncocytic neoplasms from renal cell carcinoma. A total of 57 renal tumors were prospectively collected. Histopathological analysis and radiomics data extraction were performed. XGBoost classifiers were trained using the radiomics features alone and combined with the results from the visual evaluation of Tc Sestamibi SPECT/CT examination. The combined SPECT/radiomics model achieved higher accuracy (95%) with an area under the curve (AUC) of 98.3% (95% CI 93.7-100%) than the radiomics-only model (71.67%) with an AUC of 75% (95% CI 49.7-100%) and visual evaluation of Tc Sestamibi SPECT/CT alone (90.8%) with an AUC of 90.8% (95%CI 82.5-99.1%). The positive predictive values of SPECT/radiomics, radiomics-only, and Tc Sestamibi SPECT/CT-only models were 100%, 85.71%, and 85%, respectively, whereas the negative predictive values were 85.71%, 55.56%, and 94.6%, respectively. Feature importance analysis revealed that Tc Sestamibi uptake was the most influential attribute in the combined model. This study highlights the potential of combining radiomics analysis with Tc Sestamibi SPECT/CT to improve the preoperative characterization of benign renal oncocytic neoplasms. The proposed SPECT/radiomics classifier outperformed the visual evaluation of Tc Sestamibii SPECT/CT and the radiomics-only model, demonstrating that the integration of Tc Sestamibi SPECT/CT and radiomics data provides improved diagnostic performance, with minimal false positive and false negative results.