Nephrocalcin (NC), an acidic glycoprotein produced by renal proximal tubule cells and functioning as an inhibitor of calcium oxalate monohydrate crystalization, has been previously shown to have increased urinary excretion in patients with renal cell carcinoma (RCC). The current study uses immunohistochemical techniques to localize NC to cells of primary RCC.We studied 29 kidneys removed because of RCC. Slides were deparaffinized and stained after incubating with anti-NC antibody by using the avidin-biotin-peroxidase complex techniques. Uptake of stain by tumor cells and adjacent normal renal cells was compared.Twenty-seven kidneys (93%) showed positive staining for RCC tumor cells; 2 kidneys staining positive for normal proximal tubule cells failed to stain adjacent RCC tumor cells (7%).The data suggest that enhanced production of urinary NC in patients with RCC derives from cells of the primary tumor.