Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Optical coherence tomography has been used for the diagnosis of retinal disease and has been used experimentally for imaging of vascular plaques, gastrointestinal pathology, bladder cancer, prostate cancer, and recently to examine benign kidney microanatomy. It has not been previously used to image kidney cancer. This study presents the first data on the utility of OCT in the imaging for renal neoplasms. It found that OCT was most successful in distinguishing AML and TCC from normal parenchyma. OCT had more limited success at differentiating oncocytoma. Clear cell tumors and other renal cancer subtypes had a more heterogenous appearance, precluding reliable identification using OCT. The study shows that higher resolution versions of OCT, such as OCM, will be needed to allow optical coherence imaging to reach clinical utility in the assessment of renal neoplasms. OBJECTIVEs • To determine the appearance of normal and neoplastic renal tissue when imaged with optical coherence tomography (OCT). • To preliminarily assess the feasibility of using OCT to differentiate normal and neoplastic renal tissue. PATIENTS AND METHODS • After radical or partial nephrectomy in 20 subjects, normal renal parenchyma and neoplastic tissue samples were obtained. • The tissue was evaluated with light microscopy and using a bench-top laboratory OCT system with a lateral resolution of 10 µm. • OCT images were compared with histological slides to evaluate the ability of OCT to differentiate renal neoplasms. RESULTS • Pathological subtypes included eight clear-cell, three papillary and two chromophobe renal carcinomas; two oncocytomas; one angiomyolipoma (AML); two transitional cell carcinomas (TCCs); and one haematoma. • Using OCT, benign renal parenchyma showed recognizable glomeruli and tubules. • TCC had a distinctive appearance on OCT whereas AML showed a unique identifiable signature because of its fat content. Oncocytomas had a lobulated appearance, which appeared subtly different from renal carcinoma. • Renal carcinoma lacked recognizable anatomical elements and had a heterogeneous appearance making differentiation from normal parenchyma at times difficult. • Subtypes of renal cancer appeared to vary on OCT imaging although discrimination was unreliable. CONCLUSIONS • OCT imaging for renal neoplasms was most successful in distinguishing AML and TCC from normal parenchyma and malignant tumours. Oncocytoma differed subtly from renal carcinoma, making distinction more challenging. • Clear-cell tumours and other renal carcinoma subtypes had a heterogeneous appearance on OCT, which precluded reliable differentiation from normal parenchyma and between renal carcinoma subtypes. • Higher resolution versions of optical coherence imaging, such as optical coherence microscopy, will be necessary to achieve clinical utility.