ProblemPort‐wine stains (PWS) are vascular anomalies that may cause significant functional and psycho‐social ramifications worsening by age. Traditional management of port‐wine stains involves pulsed dye laser treatments, however only 10% of these lesions show complete response and 35% of these recur even after complete response. Therefore, there is still a need for an effective treatment for PWS. Vascular endothelial growth factor (VEGF) ‐a potent angiogenic molecule‐has been shown to be associated with various vascular anomalies such as hemangiomas and arterio‐venous malformations. However, the possible pathophysiological relationship of VEGF and PWS has not been investigated previously. The purpose of this study is to investigate if VEGF and VEGF‐receptors are overexpressed in PWS as a key step in developing a potential targeted treatment approach for this disfiguring disease.Methods12 surgically resected PWS specimens and 12 normal skin specimens were immunohistochemically stained by using anti‐VEGF and anti‐VEGF receptor 2 antibodies.ResultsPWS specimens revealed significantly higher levels of expression of both VEGF molecule and VEGF‐receptor 2 than the control specimens.ConclusionVEGF and VEGF‐receptor 2 may play a role in pathophysiology of PWS. Overexpression of these molecules may suggest that PWS could have proliferating potential in addition to their hypertrophic growth pattern. Therefore, targeted approaches against VEGF and its receptors may have a potential role in the treatment of these disfiguring lesions.Significance1. Expression of VEGF and VEGF receptors in PWS has not been investigated previously. 2. The results of this study may suggest that PWS could have proliferating potential, in contrast to the common belief that PWS progress by hypertrophy rather than hyperplasia. 3. Targeted approaches against VEGF and its receptors may have a potential role in the treatment of these disfiguring lesions.SupportThis study was supported by Medical Research Endowment Award at university of Arkansas for Medical Sciences.