For these reasons, in this study, we have performed a detailed immunohistochemical analysis of TFE3 and TFEB-rearranged renal cell carcinoma compared with the most common histotypes of renal cell neoplasms evaluating its usefulness, with different cutoffs, in the differential diagnosis and looking for an immunohistochemical panel using most available markers to recognize those tumors. The gene discussed is TFE3; the disease is hereditary clear cell renal cell carcinoma.