Oral squamous cell carcinoma is a malignant tumor with poor prognosis and therefore the discovery of markers for early signs of malignant transformation would be of critical importance in clinical diagnosis. Saliva has long been tested as a valuable tool for drug monitoring and the diagnosis of systemic diseases among which oral cancer.In this study we aimed to detect the changes in ANXA1 immunoexpression in tissues of normal tongue mucosa and in induced dysplasia and OSCC. We also aimed to investigate the feasibility of using salivary ANXA1 as a cheap, rapid, simple, noninvasive biomarker for early oral cancer detection.A total of 40 rats were used in the present study, which were divided into 2 groups: a control group (20 rats with no induction) and experimental group (20 rats which received topical painting of DMBA and formaldehyde for induction of dysplasia and SCC). Rats were euthanized at 6-9, 12, 16 and 20 weeks interval from day one of carcinogens application. Tongue dissection and saliva collection were performed at euthanization dates. Salivary detection of ANXA1 by ELISA was performed, while the specimens of the dissected tongue were processed routinely to obtain 4-5μ thick sections. These sections were examined histologically by H&E stain to detect any dysplastic changes of the surface epithelium. Moreover, area percent of immunohistochemical expression of ANXA1 was measured by software Leica Qwin500.The present study demonstrated that ANXA1 was expressed in the cell membrane of normal tongue mucosa and loss of this expression was frequent in both dysplasia and OSCC. In the control group, the greatest mean area percent in tissue samples and the highest concentration in salivary samples were recorded, whereas the lowest values recorded in OSCC. A statistically significant difference in ANXA1 expression in both tissue and saliva was present between normal tongue mucosa and dysplastic