Introduction and Aim: Vascular endothelial growth factor (VEGF) as an angiogenic cytokine is a potent growth factor for endothelial cell proliferation. Its level has been proven to be elevated in systemic scleroderma (SSc) as well as in periodontitis. It was the aim of this study to demonstrate whether VEGF-levels in immunostained gingival biopsies quantified by histomorphometry may be regarded as a specific risk indicator for the progression of SSc with periodontitis in comparison to periodontitis alone. Materials and Methods: Within indicated surgical procedures biopsies were taken from 13 patients with SSc leading to 29 preparations and from 8 patients with chronic periodontitis without SSc leading to 13 preparations. Immunohistochemical testing was performed applying the monoclonal antibody anti-human VEGF Clone G 153-694 (Pharmingen, San Diego, CA92121,USA). Transverse gingival sections from each patient sample were analyzed for VEGF expression evaluation. The area of positive immunostaining in the gingival subepithelial connective tissue was measured using a microscope connected to a computerized video digital system (JAVA video analysis software, Jandel Scientific, Corte Madera, Ca) at a magnification of x100. For each sample five different areas were analyzed and the data were pooled to represent a mean value. The results were expressed in percentage of the positively immunostained area per total connective tissue area measuring 0.3615mm2. The data gained were combined in each group of patients to create a group mean and pooled estimate of standard error. The significance was evaluated applying the Mann-Whitney-U test (pResults: The mean percentage of the positively immunostained area for VEGF in SSc was 7.6%±2.2 while measuring 5.3%±1.2 for chronic periodontitis. The mean rank for SSc was 26.6 and 10.12 for periodontitis. The rank sum for SSc was 771.5 and 131.5 for periodontitis. Thus the difference was highly significant (pConclusion: Using quantitative immunohistomorphometry reveals VEGF expression in gingival biopsies to be elevated more in SSc than in chronic periodontitis. Our results suggest to use VEGF as a molecular marker to distinguish between SSc associated with periodontitis and periodontal diseases. Thus further studies have been initiated with larger groups of patients to corroborate or confute that VEGF is a sufficient parameter for risk assessement in SSc progression in comparison to periodontal diseases. Keywords: Vascular Endothelial Growth Factor (VEGF), Systemic Sclerosis (SSc), periodontitis, immunohistomorphometry