Background: Collagens are major proteins in the extracellular matrix, providing tissues with tensile strength. They are also important for cell adhesion and the invasion of malignant tumours. Methods: Thirty-nine samples of human colon (24 diverticulosis, 6 malignant tumours, 9 controls) were collected during elective surgery. Immunoassays for different domains of type I and III collagens and procollagens were used in soluble tissue extracts and trypsin digests of tissue samples. Results: The contents of cross-linked type I and III collagen telopeptides and total collagen were similar in diverticulosis and healthy tissue, whereas in malignant tissue maturely cross-linked type III collagen was scarce. Furthermore, some of the cross-linked type I telopeptide antigens were exceptionally small in size, indicating that the cross-linking of type I collagen in collagen fibres is impaired in cancer. The rate of type I collagen synthesis was clearly increased in malignancy, but not significantly in diverticulosis. However, type III collagen synthesis was increased in diverticulosis, but not in malignancy. Conclusions: In colon malignancy, the collagen cross-linking process was aberrant and the synthesis of type I collagen increased. In diverticulosis, the synthesis of type III collagen was increased, suggesting only moderately increased metabolic activity.