Background: Tight junctions (TJs) are the most apical intercellular junctions, play major play major roles in controlling apical/basolateral polarity and acting as paracellular barriers. Furthermore, they are also known to participate in the control of proliferation and differentiation. It is now well-established that dys-regulation of these functions contributes to initiation and progression of cancer. It has become clear that the claudins, members of a large family of 27 closely related transmembrane proteins, play a crucial role in formation, integrity and function of TJs. Some authors investigated the expression of claudin-1 (Cldn-1) in different human cancers. They concluded that alterations in Cldn-1 expression profiles during tumorigenesis, with both up-regulation and down-regulation of expression observed in numerous epithelial cancers in a stage-, type- and grade-dependent and tumor-specific manner. Cldn-1 has been proposed to affect the clinical features of these cancers and correlate with clinical outcome. Furthermore, it has been suggested that Cldn-1 is a prognostic marker for patient survival. Aim of the Study : This study was performed to investigate the immunohistochemical expression of Cldn-1 in OSCC and to correlate this expression with different grades in an attempt to evaluate its role in tumor treatment and prognosis. Materials and Methods : Immunohistochemical study in 30 specimens (14 specimens were well differentiated, 7 specimens were moderately differentiated and 9 specimens were poorly differentiated OSCCs). The sections were processed for the demonstration of Cldn-1 by the streptavidin-biotin immunoperoxidase technique following the manufacturer's instructions. The findings of immunohistochemistry were augmented with those of the image analyzer computer system using the Image J software (v1.46a, NIH, USA). Result : All studied specimens showed positive immunoexpression for Cldn-1 with alteration in expression/localization of Cldn-1 in OSCC cells occurs during the progression of primary tumor from well to poorly differentiated tumors. It was clear that mislocalization of Cldn-1 from the cell membrane to the cytoplasm and high grades cells expressed the highest levels of Cldn-1 and exhibited the highest rate of cellular mislocalization. Conclusion : It was concluded that Cldn-1 immunoexpression could be related to the dedifferentiation and the progression of oral cancer. Cldn-1 can be used as a biomarker for diagnostic and prognostic purposes.