ABSTRACT: BACKGROUND: Epithelial cell adhesion molecule (EpCAM) has been used as surrogate marker for the quantification of circulating tumor cells (CTC). Our aim was to prospectively study the value of a real-time RT-PCR assay for EpCAM detection in the peripheral blood and peritoneal cavity of patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). METHODS: From 48 patients with PDAC (40 resectable, 8 unresectable) and 10 patients with chronic pancreatitis undergoing pancreatectomy 10ml of venous blood was drawn preoperatively (PB) and postoperatively (POB, day 1 (D1B), day 7 (D7B) and after 6 weeks (6WB). Of all patients undergoing pancreatectomy, 40ml peritoneal lavage fluid was taken preoperatively and postoperatively. A real-time RT-PCR assay (TaqMan, ABI Prism 7700) was developed for the detection of EpCAM mRNA. To discriminate between EpCAM-positive and negative samples a cut-off was applied. Median postoperative follow-up was 24.0 months (range: 0.7 - 41.3). RESULTS: PB was EpCAM-positive (+) in 25% of patients versus 65% patients in POB (p< 0.0001). EpCAM(+) was noted at D1B, D7B and 6WB was found in 28.6%, 23.1% and 23.5% of patients respectively. Preoperative peritoneal lavage fluid was EpCAM(+) in 10.3% versus 53.8% of patients postoperatively (p<0.0001). At none of the time-points, an association was found between EpCAM positivity in blood and/or peritoneal cavity and cancer-specific or disease-free survival. Also, no significant associations were found between clinicopathological variables and perioperative EpCAM positivity. CONCLUSION: Despite a significant increase in EpCAM counts in postoperative blood and peritoneal lavage fluid this was not associated with worse prognosis after pancreatectomy for PDAC. Trial registration: Clinicaltrials.gov NCT00495924.