Expression of the pancarcinoma Thomsen-Friedenreich (TF) carbohydrate antigen or, more correctly, hapten, in colorectal carcinomas is not generally agreed on. Furthermore, its suggested role in liver metastasis so far has not been substantiated by direct immunohistochemical evidence. Cryostat sections from 52 primary tumors (20 with adjacent transitional mucosa), 22 liver metastases of colorectal carcinomas, and 17 samples of normal mucosae were examined immunohistologically with a panel of at least two monoclonal antibodies (mAbs) each to TF, to its precursor, Tn, and to sialosyl-Tn, among them two newly developed anti-TF mAbs. Of the primary colorectal carcinomas, 60% expressed TF. Staining was more intense with TF-alpha/beta-reactive than with exclusively TF-alpha- or TF-beta-reactive mAbs. Normal and transitional mucosae were negative. Liver metastases were positive for TF in a significantly higher percentage of cases (91%) than primary carcinomas. Patients with TF-positive primary tumors had a significantly higher risk to develop liver metastases compared with patients with TF-negative tumors (57% vs. 14%, respectively). Tn and sialosyl-Tn were expressed concomitantly in most primary (85%) and metastatic (95%) colorectal carcinomas. These antigens also were detected in transitional mucosae (Tn in 25%, sialosyl-Tn in 55% of cases). Normal mucosae were negative. These results prove unequivocally the presence of exposed TF epitopes in a majority of colorectal carcinomas in which both anomers of TF are expressed. These data further suggest that TF favors liver metastasis and that its expression in primary colorectal carcinomas is a significant risk factor for the development of liver metastasis.