Background: The Swiss Group for Clinical Cancer Research (SAKK) investigated the activity of bevacizumab/erlotinib (BE) in 101 treatment-naïve non-squamous stage IIIB and IV non-small cell lung cancer (NSCLC) patients in a single arm phase II trial (SAKK 19/05). We explored the effect of BE focusing on the exon intensity levels of EGFR and KRAS, a target and a prognostic gene, in these patients. Methods: The genome-wide exon expression level of 42 bronchoscopic biopsies was investigated using Affymetrix exon arrays. Unsupervised multivariate approaches, including principal component analysis (PCA) and hierarchical clustering were used to describe the exonic variations within EGFR and KRAS among patients having various EGFR/KRAS mutational status. All analyses were blinded for the mutational status and clinical outcome. Results: All probe sets measured within EGFR (n=451) and KRAS (n=261) were extracted for the purpose of the analysis. Fifty-one and 11 exonic probe sets were available within EGFR and KRAS respectively. PCA revealed a gradient of expression among patients which was homogeneous among different EGFR exons (average within-patient coefficient of variation=0.28), whereas more complex exonic variations were found within KRAS (average within-patient coefficient of variation=0.43). In contrast to KRAS, there was a trend showing an association between gender and the expression of EGFR (p=0.06). Conclusions: Using exon arrays, it was possible to assess the exonic expression level of 2 key genes involved in non-squamous NSCLC growth pathways. EGFR expression level was homogeneous among exons, advocating independence between the exon intensity level and the patient mutational status. Conversely, KRAS showed a significantly larger within-patient variation in the exonic expression level. We hypothesize that the exonic heterogeneity within KRAS provides additional prognostic information complementary to the patients’ mutational status. These results will be provided after the unblinding of the trial.