While debate continues, LCM based sample preparation would seem to be preferred where the goal is to identify tumor specific markers as it provides tumor cell enrichment. There is increasing recognition that cancer cells rely on the surrounding microenvironment to driver the cancer phenotype favouring survival, growth and spread. Tumor behaviours such as progression and prognosis are dependent on cellular interactions between tumor cells and stromal elements including immune cells and cells of mesenchymal origin. For example ��reactive stroma�� containing fibroblasts and myofibroblasts characterise numerous invasive cancers including lung cancer with bidirectional cross-talk between tumor cells and stromal elements important for fibroblast differentiation. In particular myofibroblasts and fibroblasts provide an important source of extracellular matrix proteins which are important for development of the extracellular matrix in tumor stroma. Inclusion of stromal elements in study samples is therefore important, enabling discovery of potentially important information about the tumor microenvironment. Thus, the finding of a gene expressed predominantly in the stroma alludes to the possibility of a tumor-stroma interaction generated by asbestos. A potential limitation of this study is the method of sample preparation used. As the primary aims were to identify gene expression profile differences and differentially expressed genes with potential diagnostic or therapeutic relevance, if redesigning this study we would use microdissected samples. Our results are of interest in highlighting the critical importance of methodology to interpretation of results in high dimensional gene expression studies, and of the need for verification with independent methods. Future gene expression studies should concentrate on determining their study aims and relevant methodology before embarking on microarray profiling experiments to ensure their question is answered adequately. The finding of a candidate gene primarily expressed in stromal lymphocytes rather than tumor cells suggests that study design and sample preparation methods must be considered when interpreting microarray study results. This study also calls for more research to determine the possible role of MS4A1 in ARLC given it was found in both AC and SCC. For our purposes, tumor cell enrichment by microdissection may have avoided the emergence of dominant signals from stromal elements, as illustrated by identification of MS4A1 as a gene of interest. Conversely, it also demonstrates the advantage of using macrodissection by allowing an appreciation of the contribution of stroma which is known to be important in cancer development. On the other hand, microdisection for gene expression studies enables more precise identification of gene dysregulation in lung cancer cells only; similarly for clonal cell lines.