<p>Recently, a structured approach to renal mass characterization known as the Kidney Imaging Reporting and Data System (KI-RADS) was proposed. In that proposal, the authors noted the need for imaging characteristics to be rooted in the biological underpinnings of the tumors in order to optimally risk stratify patients with indeterminate renal masses. Although multi-parametric magnetic resonance imaging may be an important initial modality for locoregional staging and lesion characterization, molecular imaging may provide more fundamental biological insight. To date, the mitochondrial imaging agent ^99mTc-sestamibi for single-photon emission computed tomography/computed tomography and the carbonic anhydrase IX-targeted monoclonal antibody ⁸⁹Zr-girentuximab for positron emission tomography/computed tomography are the best characterized radiotracers that can potentially be incorporated into indeterminate renal mass risk stratification. Both have been studied in large, prospective, scan-and-resect trials against a surgical histopathology gold standard. In this manuscript, we review the current imaging approaches to renal mass characterization; discuss the evidence for molecular imaging in this setting; explore the potential synergy among anatomic imaging, molecular imaging, and biopsy; and propose a molecular&#xa0;imaging-focused companion KI-RADS framework. We also outline future directions for integrating diverse sources of data with potential application of artificial intelligence. The molecular imaging perspective on KI-RADS translates summarized biological insights from imaging into a five-point Likert scale based on the potential for an aggressive histology for an indeterminate renal mass. Going forward, we believe that the strong correlations between molecular imaging findings and underlying tumor biology will warrant incorporation of molecular imaging techniques into any final form of KI-RADS.</p>