Proopiomelanocortin (POMC) and melanocortin 1 receptor (MC1R) are regulators of melanogenesis and pigmentation. Our objective was to estimate their levels, searching for a possible role of the melanocortin system in vitiligo. This study included 40 vitiligo patients and 40 controls. Skin biopsies were taken from lesional and non‐lesional skin of patients and from the non‐sun exposed skin of controls to detect the expression of POMC and MC1R using quantitative real‐time polymerase chain reaction. Both factors were significantly lower in lesional than non‐lesional skin and controls, while they were significantly higher in non‐lesional skin than in controls. There was a statistically significant positive correlation between lesional levels of POMC and MC1R, as well as between non‐lesional levels of POMC and MC1R in the patients. On the other hand, we found a statistically significant negative correlation between the lesional and non‐lesional levels of POMC, as well as between the lesional and non‐lesional levels of MC1R in the patients. As a conclusion, the melanocortin system could play a role in the pathogenesis of vitiligo or could be affected as the end result of the disease.