The prognosis and survival of patients with laryngeal and hypopharyngeal squamous cell carcinoma (SCC) are related to the clinical staging. Tumor growth and metastasis are closely related to angiogenesis. Vascular endothelial growth factor (VEGF) and cyclooxygenase 2 (COX-2) are intimately related to the angiogenic process in which the blood supply required for neoplastic evolution is ensured. Considering the contributions of VEGF and COX-2 to the formation, growth, and progression of primary tumors, as well as their metastasis, it has been thought that the expression of these two factors might be related to the size and/or aggressiveness of laryngeal and hypopharyngeal cancer. To test that theory, we conducted a retrospective study to evaluate the expression of VEGF and COX-2 markers in archived specimens of SCC of the larynx and hypopharynx to correlate their expression with tumor size. These specimens had been obtained from 35 patients-31 men and 4 women, aged 37 to 75 years (mean: 57)-who had been treated for laryngeal or hypopharyngeal SCC at our tertiary care university hospital over a period of 15 years. Immunohistochemical analyses were performed with avidin-biotin-peroxidase staining for VEGF and COX-2 antibodies. The degree of VEGF and COX-2 expression was based on the German scale of immunoreactivity. Specimens were separated into groups based on the intensity of expression (none/low and moderate/strong) and tumor size (TNM categories T1/T2 and T3/T4). A total of 7 patients exhibited moderate or strong VEGF expression (3 from the T1/T2 group and 4 from the T3/T4 group), and 17 patients demonstrated moderate or strong COX-2 expression (8 from the T1/T2 group and 9 from the T3/T4 group). We found no statistically significant relationship between tumor size and either VEGF or COX-2 expression. Our study demonstrated that despite the intrinsic connection between and VEGF and COX-2, neither appears to be related to the size of the SCCs of the larynx or hypopharynx. Other factors must be involved in the pathogenesis and progression of this disease, and further studies are needed to identify them.