Various tumor-associated antigens have been reported in pancreatic adenocarcinoma tissue. This study examines the incidence and co-expression of CA 19-9, DU-PAN-2, CA 125, and TAG-72 in serum and cancer tissue from patients with pancreatic cancer. In tissue, 83% of the cases demonstrated co-expression of three or more antigens. The incidence of antigen expression was comparably high for CA 19-9, DU-PAN-2, and TAG-72; however, significantly more cancer cells within each sample demonstrated CA 19-9. Serologic co-expression of elevated antigen levels was less common; only 39% of the patients showed increased circulating levels of three or more antigens. The predictive value of tissue immunoreactivity for elevated circulating levels of antigen was strongest for CA 19-9. Immunoreactivity patterns in cancer tissue suggest that the epitopes for these antigens are distinct, and DU-PAN-2 antigen was identified in patients who could not manufacture CA 19-9 (a sialylated Lea antigen). However, a strong correlation between circulating levels of CA 19-9 and DU-PAN-2 supports the contention that these two antigens are incidentally expressed on the same mucin molecule.