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BACKGROUND AND OBJECTIVE: Matrix metalloproteinases (MMPs) are a group of enzymes responsible for extracellular matrix breakdown. Increased activity of type 13 is involved in invasion of oral squamous cell carcinoma. This study was performed to compare the level of matrix metalloproteinase13 (MMP13) in saliva and serum of patients with oral squamous cell carcinoma and healthy controls. METHODS: In this experimental in vitro study, 24 saliva and 24 serum samples were collected from patients with primary oral squamous cell carcinoma after histopathologic confirmation, whereas 21 saliva samples and 21 serum samples were collected from healthy subjects with mucosal health confirmation. Clinical examination was done for MMP-13 levels in saliva and serum, and the results were compared by ELISA. FINDINGS: MMP-13 levels in serum (7.47±2.36) and saliva (8.42±2.69) of patients with oral squamous cell carcinoma compared to healthy subjects increased respectively by 5.39±1.90 and 6.72±2.11 (P= 0.002 and P= 0.025, respectively). The levels of MMP13 in saliva and serum to determine the existence of oral squamous cell carcinoma has a "good" diagnostic value, with sensitivity and specificity of 88% and 86% respectively for serum, and 88% and 71% respectively for saliva. CONCLUSION: According to the results of this study, the levels of MMP13 in saliva and serum of patients with oral squamous cell carcinoma was higher than in healthy individuals and this biomarker had good diagnostic value in the diagnosis of oral squamous cell carcinoma. [ABSTRACT FROM AUTHOR]