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At present, researchers are continually attempting to identify different tissue markers to detect and identify target molecules involved in global malice such as Oral Squamous Cell Carcinoma to understand the carcinogenetic process and possibly develop therapeutic targets. However, the majority of research in the field of Oral Pathology involves the use of conventional immunohistochemistry techniques. The tissue specimens received by oral incisional biopsies are not always generously available, thus, making consecutive sectioning of the specimen to observe multiple biomarkers infeasible. The multiplex immunohistochemistry technique allows to simultaneously observe multiple markers within a single section, thereby having an advantage of conserving biological and economical resources. Even so, it is seldom used in the field of Oral and Maxillofacial Pathology possibly because of relatively scant and scattered literature. In this context, the following report demonstrates the utility of the multiplex immunohistochemistry technique in illustrating the concomitant expression of E-Cadherin and Podoplanin in Oral Squamous Cell Carcinoma. The results of this technique demonstrated obvious benefits of the multiplex immunohistochemistry technique in which it was possible to simultaneously visualize the changes in expression of target molecules occurring during the pathologic process, thus, providing a better insight into their possible role and correlation with each other within the tumor microenvironment. It could be inferred that the multiplex immunohistochemistry technique can be utilized in the field of Oral Pathology for efficiently obtaining a more elucidative microscopic picture in other oral lesions involving complex molecular interactions such as odontogenic tumors.