Collecting duct carcinoma is a highly aggressive renal epithelial malignancy, although it accounts for less than 1% of the incidence of renal epithelial neoplasms. Differential diagnoses between collecting duct carcinoma, pelvic urothelial carcinoma with marked invasion to the renal parenchyma (invasive urothelial carcinoma), and papillary renal cell carcinoma is often challenging. In our current study, we examined the utility of using commercially available antibodies, in conjunction with lectin histochemistry, for such differential diagnoses. We examined 17 cases of collecting duct carcinoma, 10 cases of invasive urothelial carcinoma and 15 cases of papillary renal cell carcinoma (type 1, 6 cases; type 2, 9 cases) in these evaluations. Our results indicated that Ulex europaeus agglutinin 1, E-cadherin, and c-KIT were frequently positive in collecting duct carcinoma and invasive urothelial carcinoma, in comparison with papillary renal cell carcinoma, which had negative results for CD10 and alpha-methylacyl CoA racemase. We found, however, that collecting duct carcinoma showed positivity for high-molecular-weight cytokeratin and low-molecular-weight cytokeratin at a low frequency compared with invasive urothelial carcinoma, and that these distinctions need further careful evaluation. In addition, high-molecular-weight cytokeratin positivity was not a reliable marker for collecting duct carcinoma. We conclude that Ulex europaeus agglutinin 1 reactivity and positivity for E-cadherin and c-KIT are effective in distinguishing collecting duct carcinoma from papillary renal cell carcinoma, and that negative results for alpha-methylacyl CoA racemase and CD10 are potentially useful hallmarks of this distinction also. In contrast, a differential diagnosis for collecting duct carcinoma and invasive urothelial carcinoma will require careful examination of multiple routinely stained specimens, particularly in cases of in situ neoplastic lesions in the pelvic mucosa.