Background: Follicular lesions of thyroid represent a heterogeneous group of cases with varying malignant potential. Immunohistochemical (IHC) markers could be used to distinguish between equivocal, benign and malignant thyroid lesions, but no single marker is sensitive or specific enough to be used alone for this purpose. Thus, a combination of 2 or more markers may be required. Aim of Study: This study aimed to assess IHC expression of PD-L1 and HBME-1 in follicular thyroid lesions. The sensitivity and specificity of each marker alone and in combination were assessed to achieve more accurate diagnosis. Patients and Methods: This study included 70 cases of benign and malignant thyroid lesions were tested for PD-L1 and HBME-1 positivity scores based on the percentage positivity and staining intensity. A total score was obtained by adding the percentage positivity scores and intensity scores for each section. Results: PD-L1 expression was detected in 50/70 of all studied cases. HBME-1 expression was detected in 44/70 of studied cases. the combined use of both markers for diagnosis of thyroid carcinoma compared to other thyroid lesions revealed that; the sensitivity was 85.7%, specificity was 85.7%, positive predictive value (PPV) was 90% ,negative predictive value (NPV) was 80% and diagnostic accuracy was 85.7%,

Conclusion: The IHC evaluation of PD-L1 and HBME1 expression in follicular thyroid lesions demonstrates a gradual decrease in their expression from malignant lesions to low-risk lesions and finally to benign lesions. The combined use of PD-L1 and HBME-1 increases the sensitivity and specificity of diagnosis of thyroid carcinoma.