Background: Hashimoto’s Thyroiditis is an established risk factor for development of lymphoma in thyroid and because of florid lymphocytic infiltrate it becomes difficult to distinguish it from lymphoma thereby posing a diagnostic challenge. The aim of the study was to demonstrate the demographical and morphological profiles of Hashimoto’s thyroiditis and to ascertain the importance of B cell and T cell population using CD20 and CD 3 monoclonal antibodies for differentiating Hashimoto’s Thyroiditis with extensive lymphoplasmacytoid infiltrate from MALT Lymphoma. Materials and methods: The study was conducted at the Meenakshi Medical College and Research Institute Hospital from September 2011 to July 2013. A total of 40 cases were studied. The specimen consisted of partial as well as total thyroidectomy specimens. Specimens were received in formalin and sections were processed and embedded in paraffin after gross examination. Haematoxylin and Eosin staining were done as routine in all the cases. Immunoreactivity with CD20 and CD3 was graded according to the scoring system and statistical analysis was carried out using SPSS version 19.0 software with regression modules installed. Results: Correlation between cytological and histological diagnosis revealed autoimmune thyroiditis to be the most prevalent lesion followed by adenomatoid goitre with lymphoma to be least prevalent (1%). Immunohistochemical profile showed all cases(30) of Hashimoto’s thyroiditis to be positive for CD20 and CD3 positive in 29 of the 30 cases, all cases of Adenomatoid goitre (9) were negative for CD20 with single case of Lymphoma showing intensely positive for CD20 and negative for CD3. Conclusion: Strict morphological and immunohistochemical criteria are required to differentiate Hashimoto’s thyroiditis from lymphoma. Cases with florid lymphocytic proliferation and any focus of atypical lymphocytes that masks earlylymphomatous transformation should be confirmed by CD20 & CD3 as well as Kappa and Lambda immunostaining.