The growth and metastasis of many cancers is due in part to loss of cell-cell adhesion. E-cadherin, plakoglobin and beta-catenin are important in cell adhesion. Our aim was to examine the presence of these molecules in Paget's disease of the vulva and Paget's disease of the breast, and to correlate any differences in their expression with the presence of invasive disease or an underlying carcinoma. Sixty-three archival cases of Paget's disease of the vulva, including eight associated with invasive disease, and 23 archival cases of Paget's disease of breast, which included 10 cases with ductal carcinoma in situ alone, four cases with both ductal carcinoma in situ and invasive carcinoma, and five cases with underlying invasive carcinoma alone, were analysed immunohistochemically for expression of E-cadherin, plakoglobin and beta-catenin proteins. The respective mRNAs were also detected by in situ hybridisation using digoxigenin-labelled cRNA probes. Seventy-six percent (41/54) of Paget's disease of vulva cases had >50% of Paget cells expressing the E-cadherin protein, compared with 28 % (2/7) of Paget's disease vulva with invasive disease. This result was significant, with a P-value of 0.039. Twenty-five percent (14/55) of the intraepidermal Paget's disease of the vulva cases had >50% of Paget cells expressing the plakoglobin protein, compared with 12% (1/8) of cases of Paget's disease of vulva with invasive disease, and for beta-catenin, 9% (5/55) of the non-invasive Paget's disease of the vulva had >50% of Paget cells expressing beta-catenin, compared with 12% (1/8) of Paget's disease of the vulva cases with invasive disease. Sixty-five percent (15/23) of the Paget's disease of the breast had >50% of Paget cells expressing E-cadherin, and for plakoglobin and beta-catenin it was 17% (4/23) and 28% (6/21), respectively. The results were not significant. The results suggest that reduced expression of E-cadherin may have a role to play in the pathogenesis of invasive Paget's disease of the vulva. Abnormal plakoglobin expression may be involved in the formation of some cases of Paget's of the vulva and the breast.