Tissue polypeptide antigen has been advocated over the past two decades as a serum tumour marker. It was a long time before it was proven that these proteins in the serum are related to cytokeratin fragments. In this study the different behaviour of the test systems TPA, TPS, TPA(cyk) and CYFRA 21.1 were investigated in serum samples, mainly of metastasized cancer patients. By selecting individual samples with a high and a low TPA/TPS ratio it could be proven that no correlation existed in these samples between TPS (determining fragments of cytokeratin 18) and CYFRA 21.1 (determining fragments of cytokeratin 19). On the contrary, a good correlation was established between the TPA test and the CYFRA 21.1 test, and intermediate correlations were present between these tests and TPA (cyk). The TPA (cyk) test determines cytokeratin 8 and 18 fragments. During therapy, monitoring of metastasized patients with these tests could show a different pattern of reactivity. It is concluded that the different test results during therapy monitoring are not always easy to interpretate. The release of cytokeratins from cancer cells needs further study.