E- and N-cadherins are proteins involved in intercellular adhesion and are localized, e.g., in the adherens junctions of epithelial cells. Kidney tubules express these molecules in a distinctive pattern, the expression of N-cadherin being restricted to proximal tubules and that of E-cadherin to distal tubules and collecting ducts. Renal cell carcinomas (RCCs) and oncocytomas are considered to originate from these tubular epithelia. To find out whether cadherins could serve as markers for a cellular origin of these tumors, we studied the expression of E- and N-cadherins in RCCs and oncocytomas, in cell lines derived from RCCs as well as in tumors grown in nude mice. Most RCCs co-expressed E- and N-cadherins, as did 2 of the 4 cell lines studied. The expression pattern did not correlate with the histological grade of the tumors, and even the least differentiated tumors, as well as metastases, showed expression of cadherins. Renal oncocytomas expressed E-cadherin but not N-cadherin, which is in line with previous studies that have proposed a collecting duct origin for these tumors. Papillary renal neoplasms, a separate entity usually not classified as RCC, expressed neither of the cadherins studied despite the abundant expression of beta-catenin. Our results suggest that most RCCs co-express the characteristic adhesion molecules of both proximal and distal tubules, which makes it questionable whether the origin of these tumors can be reliably located to any distinct part of the renal tubule. Our results also suggest that in RCCs the increased histological grade is not directly associated with changes in the expression of either of the cadherins, indicating other mechanisms underlying the deficient capacity to form polarized tubular structures.