Background Oral squamous cell carcinoma (OSCC) is the sixth most common type of carcinoma worldwide. The pathogenic pathways involved in this cancer are mostly unknown; therefore, a better characterization of the OSCC gene expression profile would represent a considerable advance. The public availability of gene expression datasets was meant to obtain new insights on biological processes. Methods We integrated 4 public microarray datasets on OSCC to evaluate the degree of consistency among the biological results obtained in these different studies and to identify common regulatory pathways that could be responsible for tumor growth. Results Twelve altered cellular pathways implicated in OSCC and 4 genes altered in the extracellular matrix (ECM) receptor pathway were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Conclusion Using 4 expression array datasets, we have developed a robust method for analyzing pathways altered in OSCC. (c) 2011 Wiley Periodicals, Inc. Head Neck, 2011