Histological and immunohistological prognostic factors for well-differentiated oral squamous cell carcinoma (SCC) were examined in 31 patients. They included 18 males and 13 females aged 42-84 (median 63) years. The tumors were located in the tongue in 13 cases, gingiva in 7, floor of the mouth in 5, cheek mucosa in 4, and palate in 2. Advanced disease (stages III and IV) was found in 92% of patients; 22 were treated by radical surgery and nine by excisional or incisional biopsy, followed by adjuvant chemotherapy and external radiation. The 5-year survival rate in patients with stages III and IV disease was 58% and 33%, respectively. Histologic factors evaluated were tumor cell mitotic counts, degree of lymphocyte and eosinophil infiltration around the tumor, mast cell counts, HLA-DR expression on tumor cells, or surrounding lymphocytes. Multivariate analysis revealed that degree of eosinophilic infiltration and expression of HLA-DR antigen on the tumor cells were significant factors for prognosis (P < 0.05); i.e., heavy eosinophilic infiltration and expression of HLA-DR antigen on tumor cells were signs of an unfavorable prognosis. The interpretation of the present findings are discussed with a review of the literature.