Metanephric adenoma (MA) is a rare benign renal neoplasm that shares morphologic and immunophenotypic overlap with epithelial-predominant Wilms tumor (e-WT) and with the solid variant of papillary renal cell carcinoma (s-PRCC). Cadherin 17 (CDH17) is expressed primarily in the normal intestine and digestive tract tumors and has not been detected in tumors from other sites including the kidney. We investigated the diagnostic utility of CDH17 in differentiating between MA, e-WT, and s-PRCC. Immunohistochemical analysis for CDH17, CD57, AMACR, WT-1, and CDX2 was performed on 17 e-WTs, 15 s-PRCCs, and 21 MAs and assessed on the basis of a combined score of extent and intensity. Normal adult kidney parenchyma was negative for CDH17 staining. CDH17 was expressed in the late stages of fetal kidney development at the junction of the glomerular space and proximal nephron. The majority of MAs (81%) demonstrated membranous CDH17 immunoreactivity in all components (acinar, tubular, and papillary), whereas all cases of e-WTs and s-PRCCs were negative (P<0.0001). WT-1 was negative in s-PRCC and was positive in all cases of e-WT and MA. All MAs were strongly positive for CD57; however, this marker was also moderate to strongly positive in 6 (35%) e-WTs and 2 (13%) s-PRCCs. AMACR was strongly positive in all s-PRCCs, but moderate reactivity was seen in 3 (17%) e-WTs and 2 MAs (10%). CDH17 is a sensitive (81%) and highly specific (100%) marker for MA and should be considered in the immunohistochemistry panel for distinguishing MA from its mimics.