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Thyroid carcinomas are the most common endocrine tumors account for 1-2% of all malignancies. Papillary thyroid carcinoma is the most frequent type, representing more than 70% of thyroid malignancies. Although PTC has a favorable prognosis overall. However, there is a minor fraction of patients with a dismal course of disease. Proto-oncogene HER-2/neu (C-erbB2) amplification or overexpression plays an important part in tumor development, progression and aggressiveness, through direct effects on the cell cycle, angiogenesis, cellular motility and apoptosis. To study the prevalence and clinical significance of HER2 overexpression and its association with clinicopathological featuresof papillary thyroid carcinoma (PTC)in Tobruk-Libya The study group included 142 selected cases of papillary thyroid carcinoma, diagnosed at Pathology department of Tobruk Medical Center, Libya, between 2016 and 2019. All patients were surgically treated and underwent total thyroidectomy. Other clinicopathological data (gender, age, tumor size and lymph node metastasis) were extracted from medical files. All cases are stained with Hematoxylin and eosin stains and immunohistochemistry for Her2/neu. The details of 142 patients selected for analyses are as follows. The mean age of the patients at initial surgery was 36.4 years (range, 26-58 years), and 34 were (23.9%) males and 108 (76.1%) were females. 103 cases of the tumours were conventional papillary carcinomas (72.5%); 23 cases were papillary microcarcinoma (16.2%) and 16 cases were the follicular variant of papillary thyroid carcinoma (11.3%). Tumor size ranged between 2 and 42 mm, with a mean of 16.34 mm. Multifocality was present in 36 cases (25.4%) while 106 cases (74.6%) were unifocal. Lymph nodes metastasis were present in 61 cases (43%) and 81 cases (57%) shows no lymph nodes metastasis. Immunohistochemical analysis of HER2 expression was shown in all cases. While 118 cancers (83.1%) showed negative HER2 staining (score 0 and 1), there were 92 with score 0 and 26 with 1+. 22 cases showed positive HER2 immunostaining (15.5%) with 2+ and 2 (1.4%) with 3+. Total number of cases which demonstrated overexpression of 2+/3+ were 24 (16.9%). HER-2/neu can be used as prognostic marker useful for papillary thyroid carcinoma with the well-known clinicopathological prognostic factors. [ABSTRACT FROM AUTHOR]