Thyroid nodules were the extremely common endocrine tumors, in which papillary thyroid carcinomas (PTCs) were the most prevalent endocrine malignancy, representing 80-90% of all thyroid malignancies. It was still a dilemma to discriminate PTCs and benign thyroid nodules. With a new molecular genetics technology of Multiplex ligation-dependent probe amplification (MLPA), we investigated 13 PTC and 14 benign nodule tissue samples. The results showed that PTCs had more genetic copy number alteration than benign nodules (P < 0.001). Receiver operating characteristic (ROC) curve analysis suggested that genomic aberrations would provide a moderate accuracy method to discriminate PTCs and benign nodules. The gain of interleukin 13 (IL-13) gene obviously identified the great difference between PTCs and benign nodules. Immunohistochemistry also confirmed significantly higher IL-13 expression in the PTCs (P < 0.001). The current study showed that MLPA should be an effective method to diagnose PTCs and benign thyroid nodules, and also provided a clue to another relationship between IL-13 and PTCs.