Accumulating evidence points out that chemokines play important roles in colorectal mucosal immunity by recruiting leukocytes into and out of the lamina propria adjacent to the epithelium. The chemokine, CCL28, which is expressed by epithelial cells within colorectal mucosa is thought to have dual roles as a chemoattractant for leukocytes expressing CCR10 and/or CCR3 and a mediator of antimicrobial activity. To date, there is little known about the presence of CCL28 in colorectal cancer. The objective of this study was to determine whether the CCL28 protein level is altered in colorectal tumours (n=76) compared with paired normal mucosa. Further, the plasma CCL28 levels from patients with colon and rectal cancer were also examined. Immunohistochemistry revealed heterogeneous CCL28 protein expression in tumour and normal epithelial cells. Analyses by ELISA showed that the CCL28 protein level in colon tumours was significantly (P<0.001) lower than in normal tissue and that the difference in CCL28 protein level between rectal tumour and normal tissue was not significant. Patients with a tumour localized in the colon had significantly (P<0.05) higher plasma CCL28 protein levels than patients with a tumour localized in the rectum. These discrepancies may suggest that there are different mechanisms and signalling pathways involved in the pathogenesis of cancer in the colon and rectum and thereby differentially promote the expression and secretion of CCL28 protein. Further studies on CCL28 protein in colorectal cancer with an extended number of patients are necessary to conclude whether tissue levels and plasma concentrations carry significant clinical relevance.