Immunohistochemical and molecular studies to differentiate eosinophilic kidney tumors are gradually increasing. The present study investigated the role of transient receptor potential cation channel subfamily M member 4 (TRPM4), a non-selective cation channel associated with migration, proliferation and invasion in cancer cells, in this differentiation. The aim was to investigate the effectiveness of TRPM4 in differentiation of eosinophilic kidney tumors. The study included a total of 112 patients, including 97 eosinophilic kidney tumors with the diagnoses of 33 eosinophilic clear cell renal cell carcinoma (CCRCC), 35 eosinophilic chromophobe renal cell carcinoma (ChRCC), 8 papillary renal cell carcinoma type 2 (P2RCC), 21 renal oncocytoma (RO), as well as 15 papillary renal cell carcinoma type 1 to differentiate from P2RCC. For TRPM4, diffuse staining (>10%) was observed in 2 CCRCC, 15 ChRCC, 20 RO and 4 P2RCC cases. There was a significant difference between eosinophilic CCRCC and other eosinophilic tumors (P<0.05). While basolateral staining was observed in papillary tumors, membrane staining was observed in other stained cases. It was hypothesized that the use of TRPM4 along with morphological findings, cytokeratin 7 and other markers may be useful for the differentiation of eosinophilic kidney tumors.