Soluble cytokeratin 18 fragments (M30, M65) are released from human cancer cells during cell death and hold potential as biomarkers in colorectal cancer characterized by frequent metastatic spread. A total of 62 colorectal cancer and 27 control patients were included in the study. M65 (necrosis and apoptosis) and M30 (apoptosis) were quantified preoperatively (n = 62) and postoperatively (n = 31) using specific enzyme-linked immunosorbent assays. Presence of disseminated tumor cells (DTC) in the bone marrow was assessed by staining of A45-B/B3-positive cells in aspirates. M65 was significantly elevated in patients with International Union against Cancer stage I and IIA tumors compared to controls. A subgroup (19/31) exhibited a significant (p < 0.05) decrease of M65 after tumor surgery (503.9 +/- 230.7 to 342.6 + 94.8 U/l; -32.0 +/- 16.5%), in contrast to 12 patients who revealed higher M65 levels postoperatively (386.5 +/- 128.5 to 519.1 +/- 151 U/l; +37.4 +/- 32.3%). DTC in bone marrow were found in 10% (2/19) of patients with decreasing and 50% (6/12) of the patients with increasing M65 serum concentrations after surgery (p = 0.028). In conclusion, M65 as marker is likely to be valuable to identify patients with a high incidence of systemic disease.