Chronic thyroiditis may present a focal lesion, often-palpable abnormality, simulating nodular disease. The number and morphology of the Hürthle cells (HC) vary in the thyroid aspirate. Distinguishing between neoplastic and non-neoplastic HC lesions is difficult when using the fine-needle aspiration cytology (FNAC). We present the case of a 46-year-old female with a large right nodular goiter and hypothyroidism and high titer of anti-thyroid peroxidase antibody (TPO). The thyroid ultrasound showed a large well-defined nodule (more than 6.8 cm) with hypoechogenicity and microcalcification. FNAC (Mayo Clinic technique) smears revealed HC arranged in flat sheets in 75% in the sample with moderate nuclear pleomorphism, abundant granular cytoplasm showing eosinophilia and well-defined cytoplasmic borders, a lightly eccentric enlarged nuclei; the colloid was reduced and lymphocytes were also described. The final histological examination revealed that oncocyte cell proliferation is limited to the thyroid parenchyma and does not exceed the capsule and has no vascular invasion. The presence of lymphocytic infiltration and a performing FNAC (like Mayo Clinic technique) is absolutely necessary in a focal autoimmune thyroiditis in order to exclude HC carcinoma.