It has been suggested that ezrin activation plays a key role in the regulation of cancer metastasis. In this study, we immunohistochemically investigated the expression patterns of total ezrin and its two phosphorylated forms, pEzrin(- Thr567) and pEzrin(- Tyr353), in 66 samples of invasive pancreatic carcinomas and 11 samples of normal pancreas tissues. Positive expressions of ezrin and pEzrin(- Thr567) were detected in most PDAC tissues, significantly higher than that of pEzrin(- Tyr353). Furthermore, overexpression of pEzrin(- Tyr353) in pancreatic cancers was associated with positive lymph node metastasis, less differentiation, pAkt overexpression, and shorter survival times. pEzrin(- Tyr353) may be a potent prognosis predictor for pancreatic cancer.