Electron microscopy and immunohistochemical techniques are powerful tools for the determination of tissue origin. Both techniques have been used in the current experiment for histogenesis of renal cell carcinoma. Fifty kidney tumors were subjected to immunohistochemical detection for intermediate filaments cytokeratin and vimentin, which are normally expressed in epithelial tissue and mesenchymal tissues, respectively. Twenty cases of the above were examined by electron microscopy for detection of ultrastructure features. From each kidney, two specimens were taken, one from the diseased area and another far from it to serve as a control. Immunohistochemical study revealed in cases of renal cell carcinoma, cytokeratin and vimentin were expressed alone in 44% of cases, and 40% of cases, respectively. Twelve percent of cases were coexpressed with both cytokeratin and vimentin. Electron microscopic study of diseased specimens revealed the expression of desmosomes which was observed in almost all tumor specimens. The expression of the vimentin in some cases either alone or with cytokeratin was interpreted as a change in the characters of some tumor cells which indicates the need for additional techniques in such cases to get the proper interpretation. The prevalence of the expression of cytokeratin and the persistence existence of desmosomes indicate the epithelial origin of the tumor. This data is very beneficial for determination of line of therapy and follow up of the patients. The results confirm the power of combined use of both immunohistochemistry and electron microscopy in the field of histogenesis.