Loss of E-cadherin expression has been linked to the invasive phenotypes of a variety of neoplasms, including lobular breast cancer. The expression of E-cadherin in variants of urothelial carcinoma relative to usual-type urothelial carcinoma, maximum depth of invasion and angiolymphatic invasion has not been well characterized. A total of eight cases of micropapillary urothelial carcinoma, four cases of plasmacytoid urothelial carcinoma, two cases of urothelial carcinoma with signet ring cell differentiation and two cases of urothelial carcinoma with mixed plasmacytoid and signet ring cell differentiation, all obtained from cystectomy/cystoprostatectomy cases, were identified. In all nine cases of usual-type invasive and noninvasive high-grade urothelial carcinoma were also included in the study. Immunohistochemical staining of E-cadherin was performed in all cases. Pathological parameters including depth of invasion and presence of angiolymphatic invasion were documented. Maximum depth of invasion: In micropapillary urothelial carcinoma, extravesical extension was seen in three of eight cases; muscularis propria invasion in four of eight cases; and lamina propria invasion in one of eight cases. In plasmacytoid urothelial carcinoma, extravesical extension was observed in two of four cases, and muscularis propria invasion and lamina propria invasion in one of four cases each. In urothelial carcinoma with signet ring cell differentiation, extravesical extension and muscularis propria invasion was seen in one of two cases each. In urothelial carcinoma with mixed plasmacytoid and signet ring cell differentiation, muscularis propria invasion and lamina propria invasion was observed in one of two cases each. In usual-type high-grade urothelial carcinoma, extravesical extension was seen in six of nine cases and noninvasive in three of nine cases. In angiolymphatic invasion, micropapillary urothelial carcinoma was observed in eight of eight cases; plasmacytoid urothelial carcinoma in two of four cases; urothelial carcinoma with signet ring cell differentiation in one of two cases; and urothelial carcinoma with mixed plasmacytoid and signet ring cell differentiation in one of two cases. Usual-type high-grade urothelial carcinoma was seen in six of nine cases. E-cadherin expression: All eight cases of micropapillary urothelial carcinoma were positive for E-cadherin in the micropapillary component and adjacent usual-type urothelial carcinoma. The four cases of plasmacytoid urothelial carcinoma, two cases of urothelial carcinoma with signet ring cell differentiation and two cases of urothelial carcinoma with mixed plasmacytoid and signet ring cell differentiation were all negative for E-cadherin. All nine additional cases of usual-type high-grade urothelial carcinoma were diffusely positive for E-cadherin. E-cadherin is diffusely positive in usual-type urothelial carcinoma and micropapillary urothelial carcinoma, irrespective of pathological stage and angiolymphatic invasion. Loss of E-cadherin expression may be a marker of plasmacytoid and signet ring cell differentiation in urothelial carcinoma.