To identify novel genes that could be involved in oncogenesis of oral squamous cell carcinoma a microarray-based gene-expression analysis was performed using tumour samples from patients with low-stage (n=4) and high-stage (n=4) disease in a pilot study. Genes (601) were found to be significantly regulated in cancer tissue compared to adjacent intraindividual mucosa controls. Genes (25) were identified with differences in their regulation comparing samples from early-stage cancer with those from advanced disease. The gene expression pattern of 5 of 7 genes examined by real-time-PCR verified the results received from the microarray-experiment. Among these, FMO2, CPA6, TNC and SIAT1 were significantly upregulated in early disease stages. LGI1 gene expression was significantly enhanced in normal adjacent mucosa of patients with early-stage disease without showing a differential expression in carcinoma biopsies. With this pilot study several novel genes were identified, which could be related to early and late stage disease. Hypotheses from these findings are discussed and have to be confirmed in a larger study sample.