In prospectively collected sera of 161 patients with recurrent non-small cell lung cancer (NSCLC) receiving second-line chemotherapy, the courses of nucleosomes, cytokeratin-19 fragments (CYFRA 21-1), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and progastrin-releasing peptide (ProGRP) were investigated and correlated with therapy response.