Background and aim: Circulating tumor cells (CTCs) have been detected with the Celltrack Autoprep System in peripheral venous blood of patients with colorectal cancer. A cut-off of > 2 CTCs has been considered abnormal. However, there is no information on the presence of CTCs in the portal venous blood perioperatively. Therefore,, this study was designed to investigate whether CTCs can be isolated from the portal venous blood of patients undergoing curative surgery for non-metastatic colorectal cancer.Patients and methods: Patients undergoing curative open surgery for non-metastatic colorectal cancer (Stage I-III) were included in the study. The control group comprised patients undergoing a colorectal resection for benign diseases. Peripheral venous blood samples (7.5 ml) were drawn after inducing anesthesia and after skin closure. Portal venous blood samples (7.5 ml) were drawn by direct puncture of the portal vein upon entering the abdomen and then after removing the specimen. All samples were processed in a standard fashion and CTCs were detected using the Celltrack Autoprep System. Qualitative data are presented as percentage. Quantitative data are presented as mean ± standard deviation. Student's t and Chi square tests were used for statistical analysis. The study was approved by the institutional ethics committee. Results: Five patients, one man and four women with a mean age of 63.6 ± 20.8 yrs. were included in the control group. Two control patients that were discarded because of confounding diseases (penetrating active CD and large villous adenoma) had slightly elevated CTCs. Twenty five patients with colorectal cancer, 13 men (52%) and 12 women (48%) with a mean age of 71.4±10.9 yrs. were studied. All patients in the control group had two or fewer CTCs in 7.5 ml of portal blood either before or after intestinal resection. In patients with colorectal cancer, 32% had > 2 CTCs in peripheral blood before resection and 8% after resection. In contrast, twelve out of the 25 patients (48%) had >2 cells before removing the tumor. Considering the group as a whole, no difference between the preresection and postresection CTC count was seen (32.3 ± 100 vs 25.4 ± 86.7 cells; p=NS). When only patients with elevated CTCs were analyzed, twelve had high CTC counts prior to resection (66.5 ± 139 cells) and 7 after resecting the tumor (89±153 cells; p=NS). Conclusion: to the best of our knowledge, this is the first study reporting elevated circulating epithelial cells in portal venous blood of patients undergoing surgery using the Celltracks Autoprep System. The prognostic implications of our findings merit further investigation.