Morphological characteristics of the cell nucleus have long been used by pathologists in the clinical diagnosis of cancer. The nuclear matrix of the cell, the structure that serves to organize the chromatin within the nucleus, is known to reflect these morphological characteristics with regard to cell and cancer type. Monoclonal antibodies were developed to extracted nuclear matrix proteins. These antibodies were used in two-site immunometric assays to detect soluble nuclear matrix proteins in the supernatants of two dying cell lines and 15 tumor tissues. Furthermore, nuclear matrix proteins were detected at elevated levels in the sera of cancer patients compared with normal patient sera. In one assay, 63.2% of cancer sera read above 95% of normal sera, and in another assay, 73.7% of cancer sera read above 95% of the normal sera. With the development of monoclonal antibodies with greater cancer specificity, the detection of circulating nuclear matrix proteins may become an important clinical tool in the diagnosis and monitoring of cancer.