These findings include (1) ANXA2 is an interacting partner of EpCAM in the EpCAM+ ERα+ breast cancer cells; (2) ANXA2 co‐localizes with EpCAM at the plasma membrane of EpCAM+ ERα+ breast cancer cells; and (3) This co‐localization is of functional significance since EpCAM appeared to support ANXA2 to function as a co‐receptor for the tPA, and EpCAM seemed to have a regulatory influence on the expression/sub‐cellular localization of ANXA2. Here, EPCAM is linked to breast carcinoma.