We have retrospectively evaluated six serum tumor markers in 85 patients with carcinoma of unknown primary. The serum levels of carcinoembryonic antigen (CEA), CA 19-9, CA 15-3, CA 125, beta-chorionic gonadotropin (beta-HCG) and alpha-fetoprotein (AFP) were related with the histological pattern (undifferentiated carcinoma or adenocarcinoma), the number and the site of metastases, as well as the response to chemotherapy and the patients' survival. More than 40% of the patients had increased serum levels of all six tumor markers, except of AFP which was found to be increased in only 17% of them. Increased levels of CA 19-9 were related to metastatic adenocarcinoma, whereas CA 19-9 and CA 15-3 had a relationship with more advanced disease. Patients with liver involvement had higher mean levels of CEA and CA 19-9 as compared to those with nodal disease. None of these markers was found to have a predictive value for response to chemotherapy or survival. Although the present study has a retrospective nature, it allows us to conclude that patients with CUP have a nonspecific over-expression of the above serum tumor markers and that routine use of these markers does not offer any diagnostic or prognostic assistance.