Chromophobe renal carcinoma is composed of neoplastic cell showing several features similar to those found in the intercalated cells of the collecting ducts. Because the distal nephron expresses calcium-binding proteins playing a role in calcium homeostasis, we reasoned that these proteins could be expressed by chromophobe carcinoma and therefore represent a diagnostic marker. We studied the immunohistochemical expression of different calcium-binding proteins (parvalbumin, calbindin-D28K, and calretinin) in 140 renal tumors, including 75 conventional (clear cell) carcinomas, 32 chromophobe carcinomas, 17 papillary renal cell carcinomas, and 16 oncocytomas. Parvalbumin was strongly positive in all primary chromophobe carcinomas and in one pancreatic metastasis; it was positive in 11 of 16 oncocytomas and absent in conventional (clear cell) and papillary renal cell carcinomas, either primary or metastatic. Calbindin-D28K and calretinin were negative in all tumors, with the exception of two chromophobe carcinomas, four oncocytomas, and two papillary renal cell carcinomas showing inconspicuous calretinin expression. Our data demonstrate that parvalbumin may be a suitable marker for distinguishing primary and metastatic chromophobe carcinoma from conventional (clear cell) and papillary renal cell carcinoma. Moreover, they suggest a relationship between chromophobe renal carcinoma and renal oncocytoma and indicate that chromophobe carcinoma exhibits differentiation toward the collecting-duct phenotype.