Objective: Melanoma associated antigens-A (MAGE-A) expression is highly specific to cancer cells. Thus, they can be the most suitable targets for the diagnosis of malignancy. The aim of this study was to evaluate the sensitivity of multiple MAGE-A expression analysis for the diagnosis of oral squamous cell carcinoma (OSCC).Methods: Total of 70 OSSC and 20 normal oral mucosal (NOM) samples of otherwise healthy volunteers were examined for the expression of 10 different single antigens out of 12 different MAGE-A subtypes by highly sensitive reverse transcriptase polymerase chain reaction (RT-PCR) methods. The results were correlated to clinicopathological parameters of tumor samples.Results: Expression of MAGE-A was restricted to OSCC. The expression frequency of single antigen was between 10% and 55%. However, expression rate was increased up to 93% by the elevated number of genes examined. A significant correlation was found between the expression of MAGE-A and malignancy (p = 0.0001). In addition, multiple MAGE-A detection has also correlated to the incidence of lymph node metastasis, grading and advanced clinical stages.Conclusions: Analysis of multiple MAGE-A expression is more sensitive than the analysis of a single MAGE-A for the diagnostic evaluation of OSCC. Multiple MAGE-A expression analysis may be a very sensitive method to be used for the diagnosis even in the early stage of OSCC.