Primary thyroid lymphoma is a very rare disease. Here, we present a case of primary diffuse large B-cell lymphoma (DLBCL) in a 48-year-old female involving thyroid gland. The patient had thyroid swelling for 15 years which rapidly increased during last 5 months. Fine needle aspiration cytology revealed monomorphic large cells arranged discretely. The cells have high nuclear-cytoplasmic ratio with prominent single to multiple nucleoli. Aggregates of thyroid follicular cells were absent in the smears. A cytodiagnosis of DLBCL was made and a differential diagnosis of lymphocytic thyroiditis was also included. Subsequent histologic examination revealed a high-grade non-Hodgkin lymphoma (NHL). Immunohistochemistry showed the tumor cells expressing CD45, CD20, BCl-6, and tumor cells were negative for cytokeratin, epithelial membrane antigen, CD3, CD5, and CD30. Proliferative index (Ki-67) was very high (70%). Thus, a final diagnosis of NHL of DLBCL subtype was established. The patient was treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristin, prednisone) and radiotherapy. The patient is under one-year follow-up which is uneventful. Diagn. Cytopathol. 2011; © 2011 Wiley-Liss, Inc.