The relationship between tubulocystic carcinoma and collecting duct carcinoma of the kidney remains controversial. Some experts are of the opinion that the tumors are related, considering tubulocystic carcinoma to be synonymous with low-grade collecting duct carcinoma. However, others maintain that the 2 are distinct, unrelated entities on the basis of morphologic features and clinical outcome. To explore the relationship between tubulocystic carcinoma and collecting duct carcinoma, we compared the expression of several gene products at the mRNA level in cohorts of each tumor subtype. Seven cases of tubulocystic carcinoma and 8 cases of collecting duct carcinoma were identified. Total RNA was isolated from formalin-fixed paraffin-embedded tissue from each case. Relative expression levels of vimentin, alpha methylacyl CoA racemase, E-cadherin, p53, CD10 antigen, parvalbumin, cytokeratin 7, and cytokeratin 19 were assessed by quantitative reverse transcription polymerase chain reaction. Tubulocystic carcinoma was characterized by relative overexpression of vimentin, p53, and alpha methylacyl CoA racemase, compared with collecting duct carcinoma (P<0.05 for each gene, t test). In general, tubulocystic carcinoma expressed higher levels of E-cadherin and CD10, whereas collecting duct carcinoma expressed higher levels of cytokeratin 19; however, these trends did not reach statistical significance in this study cohort. Tubulocystic carcinoma and collecting duct carcinoma did not express cytokeratin 7 differentially. Case-to-case variability of gene expression limited the effectiveness of any one marker to distinguish the tumor types. Our study demonstrates that tubulocystic carcinoma and collecting duct carcinoma have different expression profiles of selected genes, including vimentin, p53, and alpha methylacyl CoA racemase. Further analysis of additional cases, using quantitative reverse transcription polymerase chain reaction and immunohistochemistry, will be useful to test the reproducibility of these findings. In addition, larger studies may establish statistical differences in expression of other genes analyzed in this study. Overall, these findings support the view that tubulocystic carcinoma and collecting duct carcinoma should be considered as 2 distinct entities at the molecular level.