A number of volatile organic compounds (VOCs) have been identified and used in preliminary clinical studies of the early diagnosis of lung cancer. The aim of this study was to evaluate the potential of aldehydes (known biomarkers of oxidative stress) in the diagnosis of patients with non-small cell lung cancer (NSCLC). We used an on-fiber-derivatisation SPME sampling technique coupled with GC/MS analysis to measure straight aldehydes C3-C9 in exhaled breath. Linearity was established over two orders of magnitude (range: 3.3-333.3×10(-12) M); the LOD and LOQ of all the aldehydes were respectively 1×10(-12) M and 3×10(-12) M. Accuracy was within 93% and precision calculated as % RSD was 7.2-15.1%. Aldehyde stability in a Bio-VOC(®) tube stored at +4°C was 10-17 h, but this became >10 days using a specific fiber storage device. Finally, exhaled aldehydes were measured in 38 asymptomatic non-smokers (controls) and 40 NSCLC patients. The levels of all of the aldehydes were increased in the NSCLC patients without any significant effect of smoking habits and little effect of age. The good discriminant power of the aldehyde pattern (90%) was confirmed by multivariate analysis. These results show that straight aldehydes may be promising biomarkers associated with NSCLC, and increase the sensitivity and specificity of previously identified VOC patterns.