CEA, CA 125, SCC, CYFRA 21-1 and NSE were prospectively studied in 211 patients with non-small cell lung cancer and compared with clinical parameters (age, sex, Karnofsky Index, symptoms and smoking status), histopathological parameters (stage, histology, tumor size and nodal involvement), biological parameters (LDH and albumin) and the therapy used (surgery, chemotherapy or radiotherapy). Tumor marker sensitivity was CYFRA 21-1: 76%, CA 125: 55%, CEA: 52%, SCC: 33% and NSE: 22%. One of the tumor markers was abnormally high in 87% of the patients with locoregional disease and in 100% of the patients with metastases. Except for NSE, all tumor markers showed a clear relationship with tumor stage and histology and therefore enabled a better histological diagnosis. Abnormal CEA serum levels were mainly found in adenocarcinomas, CA 125 in large-cell lung cancers (LCLC) and adenocarcinomas and SCC in squamous tumors. Eighty-five percent of the patients with SCC levels >2 ng/ml had squamous tumors. Likewise, CA 125 levels <60 U/ml or CEA <10 ng/ml excluded adenocarcinoma or LCLC with a probability of 82 and 91%, respectively.