Background And Objectives: Oral squamous cell carcinoma (OSCC) is the fourth leading cancer and the eighth leading cause of cancer - related death worldwide. Despite improvements in diagnosis and therapeutic concepts, the 5 year overall survival rate has not improved significantly over the last 25 years and remains around 56%. Circulating tumor cells are cancer cells detached from a primary or secondary tumor and entered the circulation, these serve as a clinical biomarker for diagnostic, prognostic and pharmacological purposes. Neoangiogenesis is essential for the growth and metastasis of solid tumors.VEGFR-2 is one of the major mediator of endothelial cell mitogenesis, proliferation and survival. Inhibition of angiogenesis by disruption of VEGFR-2 pathways, this could suppress tumors` growth by limiting their blood supply. Hence, the present study was carried out to isolate and study circulating tumor cells in different grades of oral squamous cell carcinoma from the peripheral venous blood of the patient. To assess the histological grading of oral squamous cell carcinoma by using H and E sections of the biopsy sample and to assess the immunohistochemical expression of VEGFR-2 / FLK1 in circulating tumor cells and in biopsy samples. Material and Methods: The present study consisted of 60 paraffin embedded blocks of histologically diagnosed cases of 15 well differentiated OSCC, 15 moderately differentiated OSCC, 15 poorly differentiated OSCC and 15 cases of normal epithelium. Out of 45 OSCC cases, 20 OSCC patients’ blood samples were collected and subjected to CTCs isolation using Pluriselect beads. Tissue sections of 4µm thickness of paraffin embedded tissue blocks were subjected to VEGFR-2 staining. Expression of VEGFR-2, were counted randomly in 5 high power fields(40X).Quantitative analysis of VEGFR-2 was done using image analysis (image progress software) and data obtained was subjected to statistical analysis using ANOVA and Unpaired t test. Results: Higher mean expression for VEGFR-2 was seen in PDSCC followed by MDSCC, WDSCC and the control group. The difference in mean VEGFR-2 expression was found to be statistically significant between WDSCC & MDSCC (P< 0.049) as well as between WDSCC &PDSCC (P<0.000) and between MDSCC& PDSCC (P<0.001).The circulating tumor cells (CTCs) were found in 3/20(15%) patients of OSCC. Conclusion: The expression of the VEGFR-2 was higher in PDSCC as compared to MDSCC, WDSCC and normal epithelium respectively.Circulating tumor cells were found in 3 patients of OSCC.