High [(18)F]-2-fluorodeoxyglucose (FDG)-uptake of oral squamous cell carcinoma (OSCC), assessed by pretreatment positron emission tomography (PET), has indicated poor survival of patients. In this study, we sought to elucidate the underlying pathological and biological mechanisms of the close correlation in OSCC between high FDG-uptake and poor survival. Twenty-three patients who underwent both pretreatment FDG-PET and radical surgery were evaluated. We calculated the maximum standardized uptake value (SUVmax) as FDG-uptake. Tumor thickness and depth of invasion were quantitatively measured. Pathological specimens were immunohistochemically stained with antibodies to glucose transporter-1, E-cadherin, beta-catenin, vascular endothelial growth factor (VEGF), VEGF-C and Bcl-2, and their expressions were densitometrically assessed. SUVmax was significantly correlated with both tumor thickness and depth of invasion in simple regression analysis. Patients with SUVmax12 exhibited significantly shorter 3-year overall survival than patients with SUVmax < 12. Tumors with SUVmax > or =12 showed significantly greater tumor thickness, depth of invasion and average Bcl-2 intensity than those with SUVmax<12. Furthermore, tumor thickness> or =11.4mm, depth of invasion> or =11.8mm and average Bcl-2 intensity > or =50% were significantly correlated with poor survival. These results suggest that SUVmax in OSCC is significantly correlated with pathological features, and that it is both a non-invasive and useful parameter for predicting patients' prognosis.