There are limitations in the diagnosis of thyroid nodules, especially follicular lesions, and their pathogenesis remains unclear. Insulin-like growth factor-1 (IGF-1) has been implicated in tumor cell apoptosis, transformation, invasion, and metastasis; however, its role in thyroid nodules is undetermined. The aim of this study is to investigate the relationship between expression of IGF-1 and thyroid nodule, and evaluate the role of IGF-1 in differential diagnosis and pathogenetic function of benign and malignant thyroid nodules. Sixty-two paraffin-embedded thyroid tissues from patients with thyroid nodules were selected, including 18 follicular adenomas (FA), 17 nodular goiters, 13 papillary thyroid carcinomas (PTC), 2 follicular thyroid carcinomas, and 12 normal controls. IGF-1 and IGF-1R protein and mRNA expression was detected by immunohistochemistry (IHC) and real-time quantitative PCR (qRT-PCR), respectively. Grouping comparisons were employed among the above groups based on the clinical and pathological subtypes. IGF-1 and IGF-1R expression was significantly higher in FA, nodular goiters, and PTC than that in the controls (all P < 0.01). Similarly, IGF-1 mRNA expression was also significantly higher in FA (P < 0.05), nodular goiters (P < 0.01), and PTC (P < 0.01) compared with the controls. IGF-1R mRNA expression was also significantly higher in FA, nodular goiters, and PTC (all P < 0.01) compared with the controls. Compared with FA and nodular goiters, PTC showed significantly higher IGF-1 and IGF-1R protein (P < 0.01, P < 0.05, respectively) and mRNA expression (P < 0.01, P < 0.05, respectively). IGF-1 probably plays an important role in the genesis and development of certain solid cold thyroid nodules, including PTC, nodular goiters, and FA. Detection of IGF-1 and IGF-1R expression in thyroid tissues by IHC or qRT-PCR is hard to distinguish malignant from benign lesions.