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Objective: The appropriate clinical management of indeterminate small renal masses can be improved based on accurate risk stratification. This study aimed to investigate the impact of renal function on the uptake of technetium-99m (99mTc)-sestamibi, a widely available imaging agent that can be utilized to identify oncocytomas and other benign/indolent renal masses., Methods: A retrospective cohort study was conducted, involving 100 consecutive patients who underwent 99mTc-sestamibi single-photon emission computed tomography/computed tomography. Renal function was evaluated based on creatinine levels and glomerular filtration rate (GFR). Statistical analyses, including correlation and regression analyses, were performed to explore the relationship between renal function and 99mTc-sestamibi uptake., Results: The results revealed that discrepancies can occur between imaging and pathology results, emphasizing the need for careful interpretation of imaging findings. Correlation analysis demonstrated no significant correlation between relative tumor uptake of 99mTc-sestamibi and GFR or serum creatinine levels. These findings highlight the relative independence of renal function and 99mTc-sestamibi uptake and suggest sestamibi may be of use even in patients with relatively poor renal function., Conclusions: However, further research with larger sample sizes is required to validate and generalize these findings. Ultimately, understanding the broad variety of applicability of 99mTc-sestamibi uptake for risk stratification of renal malignancy could aid in appropriate clinical decision-making., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)