Background <p>Thyroid carcinoma is a common tumor affecting the Egyptian population accounting for 2% of newly diagnosed cases of cancer in Egypt yearly and constituting 7.73% of 5 year prevalence in Egypt. Stomatin-Like Protein 2 (SLP-2) and Trophoblast Cell Surface Antigen 2 (TROP-2) antibodies are both expressed in some types of thyroid carcinomas.</p> Aim <p>To evaluate immunohistochemical expression of SLP-2 and TROP-2 in papillary thyroid carcinoma and other thyroid lesions, assess association of both immunohistochemical markers with variable demographic and histopathological parameters and assess the diagnostic utility of both markers in thyroid carcinomas.</p> Subjects and methods <p>The current study is a cross-sectional study with analytical component, performed in the Pathology laboratory of Suez Canal University Hospital on 144 samples of formalin fixed paraffin embedded blocks of thyroid cases, including 79 cases of PTC and 65 cases of other thyroid lesions during the period from January 2016 to May 2019.</p> Results <p>SLP-2 and TROP-2 have shown positive expression in 91.1% and 82.3% respectively in PTC cases. Compared to positive expressions in 38.5% and 7.7% respectively in other thyroid cases. The positivity of both markers has a statistically significant association with PTC cases, compared to other thyroid lesions p-value &lt; 0.05). The sensitivity of combined positively expressed markers is 79.75%, specificity is 98.46%, positive predictive value is 98.44, the negative predictive value is 80% and the test accuracy is raised to 88.19 for discrimination between PTC and other thyroid lesions. There was no statistically significant association between all histopathological parameters and the expression of SLP-2 and TROP-2.</p> Conclusions <p>SLP-2 and TROP-2 may be promising diagnostic markers of PTC carcinoma. Further studies are needed to fully evaluate the prognostic significance of SLP-2 and TROP-2 expression in PTC and other thyroid lesions.</p>