Cytokeratin 19 (CK19) is an acidic protein of 40 kDa that is part of the cytoskeleton of epithelial cells. It is highly expressed by all epithelial cells and represents a useful indicator of epithelial differentiation. The soluble fragment of CK19 (CYFRA 21-1) can be a useful circulating tumor marker and can be detected in the serum of cancer patients. The development of metastasis in patients with cancer of epithelial origin is due to the migration of tumor cells from the original tumor to distant organs. In order to detect micrometastasis in patients with breast cancer, we evaluated and compared CK19 gene expression using RT-PCR in blood samples collected from 80 healthy women and 80 patients with localized or metastatic breast cancer. The concentration of the soluble CK19 fragment CYFRA 21-1 was measured in serum of all study subjects by radioimmunoassay employing specific monoclonal antibodies. The relationship between the expression of this molecular marker and clinical stage, tumor differentiation and CK19 mRNA transcripts was investigated. We found that CK19 mRNA expression in blood (as a direct index of the presence of circulating tumor cells) was not correlated with CYFRA 21-1.