The alpha(v)beta(6) integrin (alphavbeta6) has been shown to be up-regulated in adenocarcinoma of the breast, colon, stomach, and ovary, generally reflecting a more aggressive phenotype. Expression in endometrial cancer has not been reported. We analyzed alphavbeta6 expression in the tissue from primary endometrial carcinomas (endometrioid type) using a mouse monoclonal antibody against human alphavbeta6, and correlated the findings with grade, stage, and nodal involvement. Normal cycling endometrium was studied for comparison. alphavbeta6 was only weakly expressed in normal epithelium and infrequently expressed in precancers, but up-regulated in the majority of endometrial carcinomas, especially with high grade. Nodal metastases strongly expressed alphavbeta6, even when the primary tumor showed only focal expression. No correlation was found between expression and depth of invasion or the presence of metastases. Overexpression of alphavbeta6 in endometrial carcinoma is common. Expression is high in metastatic lesions. The level of expression of the primary tumor was not indicative of the presence of nodal metastasis; however, the number of cases with nodal metastases was limited.