The frequency of increased EGFR-mRNA expression was determined in 57 patients suffering from NSCLC by applying quantitative real-time PCR. The findings were correlated with clinical parameters and the immunohistochemical (IHC) markers EGFR, c-erbB-2, c-erbB-3, Ki-67 and p53 on cryostat sections. Of the patients 46% showed increased EGFR-mRNA, 35% revealed an increased IHC-EGFR expression; 16% of the patients showed a combined positivity and 35% a combined negativity when applying both methods, and 17 (30%) of the cases revealed increased EGFR-mRNA without IHC-EGFR expression. This subgroup was characterised by p53 coexpression and the highest frequency of deaths (35% vs. 20%) indicating a more aggressive tumour type. In contrast to IHC - where positivity was seen predominantly in squamous cell carcinomas (48% vs. 27%) - EGFR-mRNA expression was observed equally in both histological subtypes (48% vs. 43%). PCR-EGFR and IHC-EGFR tumour typing identifies different tumour characteristics with different clinical courses. Whether this combined typing could help to identify patients who respond to anti-EGFR therapies is worth further testing.