Human chorionic gonadotropin (HCG), a classic trophoblastic marker, has been found recently in many nontrophoblastic tumors. Previously we have found elevated serum betaHCG levels in 14% of small cell lung cancer patients. The aim of the present study was to assess the frequency and clinical significance of betaHCG expression in non-small cell lung tumors and in the sera of patients. 153 non-small cell lung cancer patients entered into this study. The control group consisted of 85 patients with benign lung diseases. Serum betaHCG elevation exceeding 5 mIU/ml was found in 3.5% of patients with benign lung diseases and in 12% of lung cancer patients (p = 0.03). Tumor analysis revealed the presence of betaHCG positivity in 28% of resected lung specimens. betaHCG positivity was found more often in adenocarcinoma than in squamous cell lung carcinoma both in tissue and in serum, the differences being not significant. Elevated serum betaHCG values were found more frequently in stage IV patients than in the remainder (p = 0.03). Response to chemotherapy (partial or minor response) was obtained more often in the patients with normal serum betaHCG than in those with serum betaHCG elevation (p = 0.03). We suppose that the ability to produce betaHCG is a rare but important biologic feature of lung carcinomas combined to some extent with chemoresistance.