Squamous cell carcinoma (SCC) of the tongue is characterized by an unpredictable course, ranging from relatively benign to a high degree of locally aggressive growth and metastasis. Treatment guidelines have been developed according to TNM stage, but they do not always accurately predict clinical outcome. The aim of the present study was to evaluate the expression of the matrix metalloproteinases (MMPs) that degrade the extracellular matrices, their inhibitors (TIMPs), and angiogenic factors (factor-8 and CD-34) in tumor cells and to correlate these findings with the clinicopathological features and patient outcome. Tissue specimens from 23 patients with primary SCC of the tongue were immunohistochemically stained for these markers. High expressions of MMP-9 and TIMP-1 were detected in 60.9% and 65.2% of the specimens, respectively. Tumor invasion to adjacent muscle, lymph node metastasis, and disease status at the end of follow-up were positively correlated with the microvessel count using the CD-34 marker, but not with high expression of MMP-9 or TIMP-1. Expression of MMP-9 and TIMP-1 fails to predict aggressiveness in SCC of the tongue. However, the degree of vascularization in tumor tissue is indicative of disease aggressiveness and might be used as a basis for patient selection for more intensive therapy.