To date, only one study has investigated gene expression profile differences between primary lung cancers from asbestos-exposed individuals versus those without evidence of asbestos exposure. Wikman et al. identified a 47-gene Lomefloxacin hydrochloride signature capable of FK-3311 distinguishing ARLC/NARLC classes, demonstrating the potential to use gene expression profiling to identify asbestosrelated tumor biomarkers. We also previously found evidence that gene expression profiles differ between asbestos-related lung adenocarcinoma and adenocarcinoma unrelated to asbestos. Based on these two studies we expected that gene expression profiles would differ between squamous cell carcinomas related and unrelated to asbestos. Our results do not support this hypothesis in that Illumina microarray gene expression profiles were unable to differentiate SCCs according to lung asbestos body counts with enough sensitivity or specificity to be useful as a diagnostic test. Despite the fact that the Illumina platform has been shown to be highly correlated with Taqman technology, only two of the top six differentially expressed genes selected on p-value and magnitude of expression difference were verified by the independent method of qRT-PCR. The limited dynamic range and lower sensitivity of microarrays for gene expression may account for the different results obtained with the more sensitive qRT-PCR method. Secondly, different primer positions relative to the microarray probe locations could reduce consistency between the two methods e.g. if qRT-PCR primers are located far from the microarray probe, correlation may be weaker. We used validated primers from QIAGEN for qRT-PCR and found that they were located close to the microarray probe for 3/6 genes. Although we tried to select primers targeted to the specific transcript the array probe was designed to amplify, undocumented splice variants in some genes could allow preferential amplification of specific transcripts. Not surprisingly then, class prediction analysis failed to identify a primary tumor signature capable of distinguishing ARLC-SCC and NARLC-SCC with adequate sensitivity and specificity to be useful as a clinical test. In our microarray expression analysis of macro-dissected tumors, the finding of a gene of interest predominantly expressed in stromal rather than tumor cells raises a significant issue concerning the method of tumor sample preparation, and indicates the possibility of a stromal effect from asbestos. The effect of the proportion of stromal content on results of tumor gene expression profiling has been reported. In some studies the method of dissection was found to have only minor effects on the tumor gene expression profile. Conversely, Klee and colleagues showed that laser micro dissection was capable of identifying differentially expressed genes not identified using bulk dissection methods suggesting that LCM provides greater sensitivity for detection.