Homeobox (HOX) A10, the regulator of embryonic morphogenesis and differentiation, is aberrantly expressed in several cancer types. Our previous study using microarray technology showed that significant up-regulation of HOXA10 occurs in oral squamous cell carcinoma (OSCC)-derived cell lines compared to human normal oral keratinocytes (HNOKs). The aim of the current study was to examine the status of HOXA10 mRNA and protein expression in OSCC-derived cell lines and human primary OSCCs. HOXA10 mRNA was up-regulated in six OSCC-derived cell lines compared with HNOKs and in primary OSCCs by using real-time quantitative reverse transcriptase-polymerase chain reaction. Immunohistochemistry data indicated that HOXA10 protein expression levels were consistent with mRNA expression status in OSCC-derived cell lines and primary OSCCs. Furthermore, HOXA10 expression status was correlated with the TNM stage (P<0.05). These results indicate that HOXA10 expression could contribute to cancer progression and prognosis and that HOXA10 may be a potential diagnostic marker and a therapeutic target for OSCCs.