The specificity of monoclonal antibody-based, CA 125, CA 15-3, CA 19-9 and carcinoembryonic antigen (CEA) immunoassays were evaluated by studying how these tumor markers are expressed, using serial serum specimens from patients with breast, ovarian, colorectal, and pancreatic carcinomas. It was found that none of the monoclonal defined markers was specific for any single malignant disease. Multiple markers of increased concentration were found in all serial specimens. However, only one dominant marker was associated with each type of malignant disease. Taking advantage of the different patterns of these tumor markers expressed among different carcinomas, it was demonstrated that the specificity of these monoclonal immunoassays for diagnosis and screening of cancers could be improved if ratios of the dominant marker to other markers were determined. For example, determining ratios of CA 15-3/CEA, CA 15-3/CA 125, and CA 15-3/CA 19-9 will improve the differentiation of elevated CA 15-3 of breast carcinoma from those of colon, ovarian, and pancreatic carcinomas, respectively.