Background: Despite radical surgery 30-50% of colorectal cancer patients subsequently develop distant metastases. In these patients, neoplastic cells were disseminated either before or during surgery of the primary cancer. Appropriate detection systems for the routine clinical use to determine the extend of pre- and intraoperative hematogenic tumor cell dissemination are still missing. Soluble cytokeratin 18 (CK18; M65) and a caspase-cleaved fragment of CK18 (M30) have been used as biomarkers, corresponding to tumor cell death and apoptosis respectively. Aim of this study was to evaluate the significance of pre- and postoperative cell death measurements in serum of colorectal cancer patients.Patients and methods: M30 and M65 were quantified in serum samples pre- and postoperatively and during chemotherapy. Minimal residual disease (MRD) as negative prognostic factor was assessed by detection of cytokeratin-positive tumor cells in bone marrow aspirates and assessed by staining with the pan-cytokeratin antibody A45-B/B3 in bone marrow aspirates. A total of 73 colorectal cancer patients and 27 people without cancer were included into the study.Results: Patients with colon tumors of stages UICC I and IV had significantly elevated M30 serum concentrations compared to controls. M65 measurements showed elevated levels in UICC I and IIA, compared to normal controls (p<0.05). In 31 colon cancer patients, M30 and M65 determinations were performed prior to and seven days after tumor surgery. A group of 24 patients exhibited a significant decrease of M30 in response to tumor removal, in contrast to seven patients with either persistent or higher M30 levels postoperatively. M30 correlated significantly with the increased number of recurrences within 36 months in the group with persisting levels of M30 (4/7 versus 2/24, p = 0.032). Tumor surgery led to decreased M65 serum measurements postoperatively in a subgroup of patients (19/31), in contrast to 12 patients who revealed higher M65 levels postoperatively. MRD was proven in 10% (2/19) of the first group and 50% (6/12) of the second group (p = 0.028).In a small group of patients (n = 10) receiving capecitabine/oxaliplatin chemotherapy, M30 and M65 serum measurements did not correlate with responses, however a transient increases (+24 hours) in M30 measurements was observed. Conclusions: This proof of principle study provided evidence that determinations of peri-operative changes of serum M30 and M65 levels seem to constitute a rapid marker of postoperative systemic residual tumor load in colorectal cancer patients