Abstract Background: CD 10 was initially recognised as a cell–sur-face antigen expressed by acute lymphoblastic leukaemias, and hence it's early designation as Common Acute Lymphob-lastic Leukemia Antigen (CALLA). Also, it has been proven to be reactive in various non-lymphoid cells and tissue and different types of neoplasms. CD56 or neural cell adhesion molecule (NCAM) is a homophilic membrane glycoprotein. It is an adhesion molecule from the immunoglobulin (Ig) superfamily that is expressed normally on the surface of neurons, glia, skeletal muscle cells, and natural killer cells. Aim of Study: The aim of this work is to study the immu-nohistochemical expression of CD 10 and CD56 in malignant thyroid neoplasms and different benign lesions and assess whether CD 10 can be used as a malignancy marker in thyroid pathology and whether CD56 can be used to differentiate between follicular variant of papillary thyroid carcinoma (FVPTC) and other follicular-patterned neoplasms [follicular adenoma (FA) and follicular carcinoma (FC)]. Material and Methods: A total of 50 archived, formalin fixed, paraffin embedded tissue blocks of 50 cases of malignant thyroid neoplasms and different benign lesions. The samples were immunohistochemically analysed for CD10&CD56 expressions. A p-value of less than 0.05 was considered statistically significant. Results: Concerning CD10 immunoreactivity was statis-tically significant in the malignant lesions (91.2%) compared to benign lesions (56%) (p-value=0.004). CD10 expression was statically significant in higher tumor stages (p=0.048) and in malignant cases with positive LN metastasis (p=0.012). Concerning CD56 immunoreactivity was statistically significant in the benign lesions (93.8%) compared to malignant lesions (32.4%) (p-value=0.000). There was a statistically significant difference in CD56 immunoreactivity among follicular-patterned lesions (FA, FC and FVPTC) (p-value =0.000). CD56 expression was also statically significant in malignant cases with positive LN metastasis compared to cases not associated with LN metastasis (p-value=0.024). Conclusion: The results of the current study indicate that CD 10 might be used for differentiating benign and malignant lesions and CD56 can be used to differentiate between follicular variant of papillary thyroid carcinoma and other follicular-patterned neoplasms (follicular adenoma and follicular carci-noma.