<p>The majority of thyroid lesions are of epithelial origin that exhibit a typical follicular and/or papillary growth pattern. The occurrence of a predominantly spindle cell lesion is uncommon in the thyroid gland and is likely to be misdiagnosed in cytological or histological samples, which may impact patient management. The diagnosis is made by finding a significant amount of spindle cells, which may be combined in some cases with other morphologic features. It is important to recognize if these spindle cells have benign or malignant features. The differential diagnosis for such lesions includes mesenchymal neoplasms (e.g., solitary fibrous tumor) and non-mesenchymal tumors (e.g., anaplastic thyroid carcinoma). The morphologic interpretation of such lesions can be problematic due to their rarity, pathologists’ limited experience, overlapping cytomorphologic features, and challenges selecting and interpreting appropriate ancillary studies. This review discusses most of the thyroid entities showing spindle cell features, emphasizing their cytological and histological findings of relevance to the recent Bethesda system for reporting thyroid cytopathology and WHO classification of endocrine tumors.</p>