Anaplastic thyroid cancer arises, or transforms, from pre-existing differentiated thyroid cancer. E-cadherin functions as a cell–cell adhesion molecule that complexes with catenin proteins for function. The objective of this study was to evaluate the change in E-cadherin/β-catenin expression in the transformation of differentiated to anaplastic thyroid carcinoma. A tissue microarray was constructed from 12 anaplastic thyroid tumors and their adjacent associated differentiated foci. Immunohistochemistry was used to evaluate tumor expression of E-cadherin and β-catenin. There was decreased expression of E-cadherin and β-catenin by the anaplastic tumors when compared with the differentiated thyroid tumors from which they evolved. The expression of E-cadherin and β-catenin was 92% and 67%, respectively, by the differentiated thyroid carcinoma, and 17% and 50%, respectively, by the anaplastic tumors. This report shows that derangement of the E-cadherin/catenin complex is associated with the transformation of differentiated into anaplastic thyroid carcinoma.