Skin tags are benign connective tissue tumors of the dermis of unknown etiology. Type 2 diabetes mellitus and obesity are associated with insulin resistance and hyperinsulinemia. Hyperinsulinemia may favor skin tags development through activation of insulin-like growth factor I receptors on the surface of fibroblasts and stimulation of epidermal proliferation. Mast cells play an important role in different conditions including tumors and tissue fibrosis. They produce a number of multifunctional cytokines which stimulate fibroblast and keratinocyte proliferation. The aim of this work is to evaluate the role of mast cells in skin tags of diabetic and non-diabetic patients. Thirty patients (15 diabetic and 15 non-diabetic) were the subject of our study. The clinical data were collected, biopsies were taken from large, small skin tags and adjacent normal skin. Staining with toluidine blue and mast cell count was done. Our results showed an increase in mast cell count in all skin tags examined in comparison to adjacent normal skin suggesting an important role of mast cells in the pathogenesis of skin tags. There was no significant difference between mast cell count in skin tags in the non diabetic and diabetic groups. This implies that mast cells play an important role in the pathogenesis of skin tags in addition to the role played by insulin. There were no similar studies in the literature to compare with our results.