Background and objective: The cause of skin tags (ST) remains elusive. The present study was designed to elucidate the role of leptin and to unravel other potential aetiological factors in the pathogenesis of ST. Methods: The study population comprised 58 patients with ST and 24 control individuals. Demographic and other variables were recorded. A detailed laboratory evaluation including serum leptin was performed. Results: Statistical analysis revealed significant differences between the two groups in terms of body weight, body mass index (BMI), family history of ST, triglyceride, cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL) and serum leptin levels. A family history of ST was the most important predictor of ST development by logistic regression analysis. Conclusions: These findings indicate that ST correlate with serum leptin levels and that leptin resistance may be involved in the pathogenesis of ST in susceptible individuals.