Previous studies suggested that estrogen might have an important role in thyroid nodule formation. Besides, it was recently reported that women with uterine fibroids, which estrogen has effects on, had an increased incidence of thyroid nodules. Our study was to identify the relationship between uterine fibroids and thyroid nodules and to find the factors that may have influences on the occurrence of thyroid nodules. We reviewed the records of 1144 participants who attended health check-ups from 2005 to 2008. Evaluated clinical variables included the size and number of thyroid nodules, presence of uterine fibroids, menopausal status, BMI, smoking, alcohol, medication status, serum levels of cholesterol, LH, FSH, and estradiol. A total of 925 participants were included and 163 (17.6%) subjects had thyroid nodules and uterine fibroids simultaneously. A significant association between both diseases existed (P=0.010), and closer relationship was observed in premenopausal women (n=445, P=0.001). In univariate analysis of systemic E2 level and the incidence of thyroid nodule in premenopausal women, systemic E2 levels had inverse correlation with the incidence of thyroid nodules (P=0.024, OR=0.631, CI: 0.424-0.940). In multivariate logistic regression analysis, older age and the presence of uterine fibroids were the independent factors for the presence of thyroid nodules. Our study suggested that uterine fibroids in women were definitely associated with thyroid nodules and estrogen might have a pivotal role in occurrence of both uterine fibroids and thyroid nodules.