Serum CASA, CEA, CYFRA 21-1, NSE, MSA, TPA, and TPS were determined in patients with lung cancer (LC), benign lung disease (BL), and healthy control (HC) donors. Using predefined cutpoints, the cytokeratin-related markers TPA, TPS, and CYFRA showed the highest sensitivity in non-small cell lung cancer (TPA 69%, TPS 63%, CYFRA 54%), while NSE gave the highest sensitivity in small cell lung cancer (50%), indicating that these markers may be most appropriate in monitoring the course of disease and the patients response to therapy. Receiver-operator analysis was performed to compare assays at the same specificity. At high specificities (greater than or equal to 95%), CYFRA was significantly better than all assays except CASA in the LC vs. HC and LC vs. non-infectious BL comparisons (p<0.05), while CEA was the only assay which was not significantly different to CYFRA in the LC vs. BL comparison. CASA was of particular value when used in combination with these markers, as the sensitivity was increased. In addition, pretreatment CASA was the best indicator of patient survival (one year survival of 83% for patients with CASA <5 units/ml and 10% for patients with CASA greater than or equal to 5 units/ml).