MicroRNAs (miRNAs) are the key regulators of a variety of biological processes such as cell proliferation, apoptosis and tumorigenesis. It was also demonstrated to target tyrosinase, which plays an important role in melanin synthesis. The aim of this work was to evaluate microRNA 196a-2 polymorphism and serum tyrosinase levels in vitiligo patients.The current study was a case-control study that was conducted on 100 participants. Fifty of them were patients with vitiligo, and they were located in group 1. Group 2 contained 50 age and sex matched healthy control participants. Approval of the Local Ethics Committee on Research involving human subjects of Benha Faculty of Medicine and written informed consents of participants were obtained before samples collection. Serum tyrosinase level and microRNA 196a-2 polymorphism were evaluated in all participants.The level of serum tyrosinase is significantly higher in patients with vitiligo when compared to the control subjects. T allele and TT genotype of miRNA 196a-2 polymorphism were found to have a significant relation to the development of vitiligo. MiRNA 196a-2 TT genotype and the high serum tyrosinase levels may play a role in vitiligo pathogenesis.