Objective: To avoid unnecessary surgical treatment of small renal masses (=4cm), a more accurate diagnostic method would be desirable since radiological differentiation between malignant and benign is difficult and nondiagnostic biopsies account from 9% to 37%. Optical coherence tomography (OCT) measures backscattered light versus depth, with an attenuation coefficient (µt) that may vary among different histological types. We hypothesize that quantitative measurements of µt using OCT can differentiate between normal renal parenchyma and renal cell carcinoma (RCC). Materials and Methods: Both normal and tumor renal tissues (RCC) were harvested after partial or radical nephrectomy. Analysis of µt was based on difference of (1) µt between normal and tumor tissue across all patients and (2) µt between normal and tumor tissue within individual patients. Results: Tissue samples of 18 patients were measured, of which 4 were excluded (urothelial carcinoma, oncocytoma, and benign lesion without normal tissue available). Of the remaining 14 patients, 8 contributed with both normal and RCC tissue and 6 with only normal or RCC tissue. Independent observation showed a significant difference between the median µt of normal renal tissue (4.95mm-1) and the median µt of RCC (8.86mm-1). No statistically significant difference was found when comparing the difference in µt between normal renal parenchyma and RCC within individual patients. Conclusion: There is a significant difference in µt between normal and RCC tissue across all patients. These results overpower the lack of significant difference within individuals, encouraging further research and suggesting a possible role for OCT in the diagnostic work-up of renal masses.