MUC1 (epithelial membrane antigen) is a membrane-associated mucin known to interfere with both cell-cell and cell-matrix adhesions. Overexpression has been associated with poor prognosis in a variety of cancers. We investigated the expression of MUC1 (using two different antibodies, MA695 and E29) and E-cadherin in renal cell carcinomas (137 conventional, 23 chromophobe, 20 papillary, and eight unclassified tumors) with respect to diagnostic and prognostic significance using a tissue microarray technique. Immunoreactivity was correlated with histological subtype, pT-stage, and grade using the chi2 test or the Fisher's exact test, respectively. Impact on disease-free survival was analyzed using the Kaplan-Meier method and the log-rank test. Immunoreactivity of more than 10% of cancer cells with MA695, E 29, and E-cadherin antibodies was found in 112/133 (84%), 86/133 (65%), and 7/131 (5%) conventional, 20/22 (91%), 19/22 (86%), and 21/22 (95%) chromophobe, 13/20 (65%), 8/20 (40%), and 3/20 (15%) papillary as well as 5/8 (63%), 5/8 (63%), and 4/8 (50%) unclassified carcinomas, respectively. The two different MUC1 antibodies yielded comparable staining results. A diffuse cytoplasmic staining pattern for MUC1 was found exclusively in chromophobe carcinomas, whereas conventional and papillary subtypes showed predominantly membranous staining (P<0.0001). Regarding papillary carcinomas, MUC1 was predominantly associated with type 1 (P=0.0001), and E-cadherin with type 2 (P=0.049) tumors. The cellular staining pattern of MUC1 in conventional tumors was related to pT-stage (P=0.002) and tumor grade (P=0.001): Low-stage (pT1/pT2) and grade (G1/G2) tumors showed a predominantly apical membranous staining, high-stage (pT3a/pT3b) and grade (G3/G4) tumors a predominantly circumferential membranous staining (with or without additional diffuse cytoplasmic immunoreactivity), which, in the conventional subtype, was associated with poor prognosis (P<0.0001). In conclusion, MUC1 and E-cadherin are diagnostically and prognostically useful markers in renal tumor pathology, especially when cellular staining patterns are considered.