Background: Thyroid nodules are a common clinical finding and differentiating benign ones from malignant ones is a clinical challenge. The aim of this study was to compare the rate of thyroid malignancies in patients with single thyroid nodules (STN) and multi-nodular goiter (MNG).Methods: This retrospective study was conducted on 200 patients who underwent surgical thyroidectomy, between 2008 and 2010, in Shariati hospital, affiliated with Tehran University of Medical Sciences. Data analysis performed using SPSS (version 13).Results: Of these, 63 patients (12 male and 51 female) had STN and 137 subjects (28 male and 109 female) were MNG. The mean ± standard deviation of age in patients with STN and MNG were 39.1 ± 7.1 and 42.7 ± 6.2, respectively. The two groups had no significant difference in age or sex. The rate of thyroid malignancies in patients with MNG and STN were 34.4% and 36.5% respectively, showing no significance difference.Conclusions: The study did not show any statistically significant difference between the frequency of malignant and benign nodules in single and multiple thyroid. Therefore, performing accurate pathologic assessment is recommended for all cases of thyroid nodules (MNG or STN)