Background: Vitiligo is an acquired depigmenting disorder due to destruction of melanocytes. Although many theories have been suggested for its pathogenesis, the role of autoimmunity is the most popular one. The association of vitiligo with autoimmune thyroid diseases and the increased prevalence of autoantibodies including thyroid autoantibodies in vitiligo favor this role. Our objective was to compare the frequency of thyroid peroxidase antibody (anti-TPO) in vitiligo patients with healthy subjects in Iran. Methods: Ninety-four cases of vitiligo (46 female and 48 male) and 96 control subjects (49 female and 47 male) were enrolled in this controlled study. Patients with known thyroid disease, history of thyroid surgery and those receiving thyroid medications were not included. The two groups were matched regarding gender and age. The demographic data, symptoms related to thyroid diseases and results of skin and thyroid examinations were recorded in a questionnaire for each subject. Thyroid function tests including free T3, free T4 and TSH-IRMA were performed. Anti-TPO levels were assessed as well. The collected data were analyzed by SPSS version-II in vitiligo patients and subgroups according to gender, age, extent, and duration of the disease compared with the control group. Results: Anti-TPO was detected in 17 (18.1 %) of patients affected by vitiligo, while this figure was 7 (7.3%) in the control group; the difference was significant with p-value < 0.025 (Phi & Cramer's V = 0. 162). When analyzing subgroups, the difference in the frequency of anti-TPO remained significant only in females (p-value < 0.044) (Phi & Cramer's V = 0.207) and in patients in the age ranges of 18-25 (p-value < 0.05) (Phi & Cramer's V = 0.28) and 26-35 year-old (p-value < 0.042) (Phi & Cramer's V = 0.304). The difference of the frequency of anti-TPO was not significant regarding the duration and extent of vitiligo. In addition, there was no significant difference in the levels of free T3, free T4, and TSH in vitiligo patients compared with the control group. Conclusion: According to our study, anti-TPO was shown to be significantly more common in vitiligo patients especially in young women, compared with control group. As this antibody is a relatively sensitive and specific marker of autoimmune thyroid disorders including Hashimoto thyroiditis and Graves' disease, and considering the fact that vitiligo usually precedes the onset of thyroid dysfunction, periodic follow-up of vitiligo patients for detecting thyroid diseases is further emphasized especially in young women with increased level of anti-TPO. © 2006 Daneshpazhooh et al; licensee BioMed Central Ltd.