Abstract: To investigate the clinicopathologic features, diagnosis, and differential diagnosis of anaplastic thyroid carcinoma with squamoid cell component ( ATC-SCC ). Methods: The data of 85 cases with rare thyroid neoplasms were retrospectively analyzed. Morphological observation of the sections from all cases was conducted after H&E staining. Five cases of ATC-SCC, 6 cases of thyroid squamous cell carcinoma ( TSCC ), 8 cases of with thyroid carcinoma showing thymus-like differentiation ( CASTLE ), and two cases of calcitonin-negative neuroendocrine tumor of the thyroid gland ( CNNETT ) were selected. Immunohistochemistry ( SP method ) was performed using 9 markers, namely, cytokeratin ( CK ), vimentin ( VM ), chromogranin A, synaptophysin, CD117, CD5, calcitonin, thyroglobulin, and thyroid transcription factor-1. The results of the immunohistochemical staining were analyzed. Results: Three of the 5 patients with ATC-SCC were female. The average age of the patients was 53.2 years ( ranging from 41 to 79 years ). Three lesions were located in the right lobe, whereas 2 were in the left lobe. The clinical manifestations showed a painless neck mass. Tumor size was usually large, and the texture was hard. The tumor was adherent with peripheral soft tissues. Histologically, the tumors consisted of an admixture of spindle, pleomorphic giant, osteoclast-like, and squamoid cells. On occasion, the tumor cells showed eosinophilic cytoplasm with a rhabdoid-like appearance. Hemorrhage and necrosis were common in all tumors. Immunohistochemistry showed that the cells in all 5 ATC-SCC cases were positive for CK and VM. Differential diagnosis was also conducted in the TSCC, CASTLE, and CNNETT cases when the squamoid cells were presented as the main components in the tumor. Conclusion: ATC-SCC mainly occurs in aged people, usually in females. Characterized by fast growth in most of patients, the tumor usually infiltrates the surrounding tissues, such as the extrathyroidal soft tissue of the neck. The prognosis of ATC-SCC is very poor, and multi-modality therapy, including surgery and chemoradiotherapy, may offer hope for long-term survival.