In spite of the progresses achieved in surgical treatment, radiotherapy and chemotherapy, the survival rate in oral squamous cell carcinoma (OSCC) remain unchanged among past three decades, which made this neoplasia a major problem of health in the entire world. There were investigated 42 cases of OSCC with different sites and various grades of differentiation, by histological and immunohistochemical techniques (by LSAB/HRP method), using E-cadherine and CD44. Considering the differentiation grade, the cases were histopathologically classified as 9 cases of well-differentiated squamous carcinoma, 14 cases of moderately differentiated squamous carcinoma, and 19 cases of poorly differentiated squamous carcinoma. The E-cadherine immunoexpression study indicated an immunostaining degree 3 in well-differentiated squamous carcinoma, 2 in moderately differentiated squamous carcinoma, and 1 in poorly differentiated squamous carcinoma. The results of CD44 immunostaining indicated in most of the cases an immunostaining degree 2, especially in moderately differentiated OSCC. The immunostaining degree 3 corresponded to nine cases of well-differentiated OSCC, and other two cases of moderately differentiated OSCC. Immunostaining degree 1 corresponded to poorly differentiated OSCC. The results indicate the possibility of using the two-immunohistochemical markers as prognostic factors in OSCC.