Primary squamous cell carcinoma of the thyroid (PSCCT) is a rare malignant disease with rapid fatal prognosis. The onset is generally characterized by sudden bilateral latero-cervical lymphadenopathy. The Authors report patient of 58-year-old who referred for evaluation of rapidly aggravating bilateral latero-cervical lymphadenopathy. The US highlighted the presence of a hypoechoic nodular lesion characterized by peri and intra-nodular vascularization. Multilayer CT showed diffused involvement of mediastinal and bilateral latero-cervical lymph nodes, with no evidence of primary pulmonary neoplasia or elsewhere. The patient underwent total thyroidectomy. The peri-isthmic tissue was removed due to the presence of a small roundish formation, that was due to lymph node metastasis at histological examination. Histological diagnosis: PSCCT. The immunohistochemical panel of the thyroid lesion was indispensable for the differential diagnosis between PSCCT, medullary carcinoma, anaplastic carcinoma, and thyroid metastasis of neoplasia with unknown primitiveness. The patient underwent chemotherapeutic treatment with Carboplatin and Paclitaxel with modest improvement of dysphagia symptoms and reduction of 10-15% of the target lesions. The clinical course was characterized by loco-regional progression of the disease with exitus in 10 months after diagnosis. Survival and quality of life after surgical therapy and chemotherapy were like that of patients undergoing only chemotherapy. Due to the extreme rarity of the neoplasia, 60 cases described in Literature, no exclusive guidelines are reported for PSCCT. More extensive case studies are needed to evaluate the effects of total thyroidectomy with intent R0/R1 on improving survival and quality of life of patients with PSCCT