Vascular Endothelial Growth Factor (VEGF) is closely related to tumour progression and prognosis. This study aims to evaluate the pattern and clinical implication of VEGF expression in benign and malignant neoplasms and to determine the effect of surgery on serum level of VEGF. Cases were drawn from among histologically confirmed orofacial tumours, while controls were from consecutive, ambulatory dental patients at the University of Benin Teaching Hospital. Blood samples taken from cases and controls, preoperatively and at one -month post-surgery, were allowed to clot and the serum aliquots stored at -600C till analyses. Serum VEGF was analysed using Sandwich ELISA and mean levels as well as median were measured. Spearman correlation was estimated, t-test measured significance (at p ≤ 0.05). Eighty-one subjects were studied (55 cases and 26 controls). Preoperatively, there were significantly different serum levels of VEGF in benign (48.11 ± 25.19 pg/ml) vs. malignant cases (1065.00 ± 412.14 pg/ml), and when compared with controls (45.42 ± 29.83 pg/ml), p <0.001. After definitive surgical intervention, there was a significant reduction in the level of serum VEGF in both benign (45.50 ± 24.71 pg/ml) and malignant cases (51.22 ± 16.84 pg/ml), p <0.001. One-way ANOVA revealed no significant differences between cases and controls post-surgery. There was elevated levels of serum VEGF in benign and malignant orofacial neoplasia. Surgery caused a significant reduction of circulating VEGF to normal levels irrespective of age, gender, previous medical history, perceived duration of the lesion and lymph node involvement.