This study aimed to investigate the value of repeat ultrasound-guided fine-needle aspiration (FNAC-US) in benign thyroid nodules and determine the ultrasound (US) predictors of malignancy in this group of nodules. The authors studied 35 of 143 nodules with initially benign cytological result who underwent serial re-biopsy (FNAC-US). By means of surgery, malignancy histology results were confirmed in 10 (28.5%) cases (G1) versus 25 (71.5%) benign nodules (G2). The clinical, lab, scintigraphyc, and US features were compared between the two groups to predict malignancy in thyroid nodules with initially benign cytological result. The cytological finding of 28/35 nodules were change to indeterminate cytology (Bethesda system category III or IV) at second and/or Cthird cytological study. In this group of 28 cases, 23 (82.1%) was identified until the third procedure. The interval between first and third re-biopsy was 13 months (median). There were no differences in age, gender, thyrotropin (TSH) levels, thyroid auto-antibodies, or thyroid dysfunctions. The scintigraphy showed cold nodule in 80% of G1 versus 78.9% of G2 (NS). Sonographic studies showed malignant suspected US features in G1: microcalcifications, central flow, hypoechogenicity, and border irregularity. This study suggests repeating FNAC-US in nodules with first benign cytologic result and suspicious US features of malignancy for at least two times (until the third FNAC) in about 13 months horizon.