Multivariate analysis showed that microcalcification (p = 0.037, OR = 2.260, 95% CI: 1.051–4.860), shape (p = 0.003, OR = 4.367, 95% CI: 1.629–11.705), diameters (p = 0.002, OR = 0.278, 95% CI: 0.123–0.631), anti-thyroglobulin antibodies (TGAb) (p = 0.002, OR = 0.150, 95% CI: 0.046–0.494), anti-thyroid peroxidase antibody (A-TPO) (p = 0.009, OR = 4.784, 95% CI: 1.486–15.401), and nodule goiter (p < 0.001, OR = 0.100, 95% CI: 0.046–0.217) were independent malignant risk factors in patients with thyroid nodule classified as Bethesda category III. This evidence concerns the gene TPO and thyroid nodule.