Purpose: The aim of this study was to investigate the immunohistochemical expression of CD34 and E-Cadherin among the studied cases of OSCC, Furthermore, the correlation between expression of CD34 and E-Cadherin in OSCC was evaluated to assess the contribution of different grades of OSCC to angiogenesis and loss of epithelial cell adhesion.  Also, assess the expression of CD34 and E-Cadherin in OSCC in relation to the available clinical data. This approach may be a basis to determine the prognosis of the OSCC cases. Methods:Immunoexpression of CD34 and E-cadherin antibody was evaluated in previously diagnosed, paraffin-embedded sections of 40 tissues each of well-differentiated, moderately differentiated OSCC and poorly differentiated OSCC. Three high power fields of tumor were counted for each sample stained by CD34. Moreover, a total mean of three fields was calculated to calculate MVD of the samples. Three high power fields at the invasive front of the tumor were counted for each sample stained by E-Cadherin. Results: Increased expression of CD34 and decreased expression of E-Cadherin was found to be correlated significantly with clinical factors and a poor prognosis. there is a statistically significant association between OSCC grade and CD34 and E-Cadherin expression. Conclusion:  Increased expression of CD34 and reduced expression of E-cadherin may be a reliable indicator of increase in the invasiveness of OSCC and poor prognosis.