Tumors require a blood supply for growth and hematogenous dissemination. Angiogenesis is one of the mechanism by which tumors acquire their microcirculation. Structurally and functionally, these newborn vessels are abnormal, showing increased permeability, delayed maturation, and potential for rapid proliferation. Such vascular defects could be an explanation for the aggressivity of oral squamous cell carcinoma (OSCC). For these reason we studied the morphology of tumoral vessels in such tumors by using immunohistochemistry and immunofluorescence. Forty formalin-fixed, paraffin-embedded tissue blocks of OSCC were processed for double enzymatic and fluorescence immunohistochemistry. We were interested in analyzing the tumor vessel architecture, and their maturity and activity in such tumors. The tumor vessel architecture had a chaotic pattern, mostly of different sizes, aberrant morphology, tortuous, without clear lumen, and irregularly branches. Regarding pericytes recruitment, the immature and intermediate vessel types (both negative to smooth muscle actin-SMA) were the most numerous type of tumoral vessels. The mature ones (positive to SMA) were readily more numerous at the invasive front of OSCC (85.4 vessels/4 mm(2) +/- 38.3), especially in poor differentiated tumoral type. Investigation of the tumor vessel basal membrane, as reactivity for collagen IV, revealed variability in thickness (2.59 microm +/- 0.48), small surface projections, discontinuities and loose associations with endothelial cells; these abnormalities being more obviously at the tumor-host interface and in poor differentiated OSCC. The most active angiogenesis was noticed in poor differentiated OSCC (0.23 +/- 0.04), at the tumor-host interface with the immature and intermediated vessel as the most active tumor vessel types. In conclusion, our study revealed some peculiar structurally and functionally defects of tumor vessels in OSCC, changes that could be selective targets for the new developing antiangiogenic drugs.