Positive staining with Hale's colloidal iron stain, or modifications thereof, is considered a diagnostic feature for chromophobe renal cell carcinoma and has been used as a discriminatory feature to differentiate it from other renal tumors. We studied colloidal iron staining in 62 cases encompassing a wide histologic spectrum of renal neoplasms (14 chromophobe renal cell carcinomas, 19 renal oncocytomas, 11 each of granular variants and conventional clear cell renal cell carcinomas, and 7 eosinophilic variants of papillary renal cell carcinoma) to investigate the specificity of the stain for chromophobe renal cell carcinoma. In cases of chromophobe renal cell carcinoma, sections from two different areas were stained to ascertain whether there was any spatial variation in staining. Influence of staining techniques on the results also was investigated by staining each case of chromophobe renal cell carcinoma using two different methods: the traditional Hale's and a modified Mowry's technique, which treats sections with 3% acetic acid before adding the colloidal iron. Our results show that positive staining with colloidal iron stain is not limited to chromophobe renal cell carcinoma, however, a diffuse and strong, reticular staining pattern was observed only in cases of chromophobe renal cell carcinoma (14 of 14). The staining patterns were less consistent in all other renal neoplasms and differed from the reaction observed in chromophobe renal cell carcinoma. Most renal oncocytomas (16 of 19) had focal and weak, fine dustlike positivity, and all clear cell carcinomas showed focal, coarse, dropletlike positive staining (22 of 22), in addition to a focal, coarse, bubbly pattern in 5 of 11 clear cell subtypes. Although all seven cases of the eosinophilic variant of papillary renal cell carcinoma showed strong, coarse, dropletlike staining, most of the positivity was coincident with the Perl's (prussian blue) reaction, indicating that the staining was due to hemosiderin, which is frequently present in this histologic subtype of renal cell carcinoma. Staining intensity did not vary considerably among different areas of chromophobe renal cell carcinoma, but the modified Mowry's method yielded brighter and sharper reticular staining, as compared with the Hale's method. Our results show that in the appropriate morphologic context diffuse and strong reticular positivity using the modified Mowry's colloidal iron stain method is highly characteristic for chromophobe renal cell carcinoma. Treatment of sections with 3% acetic acid before adding the colloidal iron gives technically superior staining results.