Salivary gland cancers (SGCs) are rare representing only 5% of head and neck neoplasms. They present the most diverse group of neoplasms having biological, histological and clinical diversity. This diversity represents a challenge for diagnosis, classification and management of salivary gland cancers. Mucoepidermoid carcinoma (MEC) represents 10-15% of all salivary gland tumours and 30% of salivary malignancies. It is considered to be the most common malignancy of major and minor salivary glands of both children and adults accounting for 12% to 40% cases worldwide. According to the WHO, MEC is classified into three grades: low (LG-MEC), intermediate (IMG-MEC), and high grade (HG-MEC). These three grades have different clinical and biological diversity, therefore they show major differences in their outcome. Correct histopathological diagnosis thus remains vital. While Adenoid cystic carcinoma (AdCC) is a rare epithelial tumor that accounts for 1% of all cancers of the head and neck region. It is the second most common salivary gland cancer, comprising7.5% of all salivary gland cancers. The tumor is classified into 3 different variants: cribriform, tubular and solid variants. Each may occur separately or different forms can exist in the same tumor, with the solid being the most aggressive type. EpCAM is a 40 kDa type I transmembrane glycoprotein expressed on most normal and cancerous epithelial tissues, cancer stem cells, embryonic stem cells and germ cells. EpCAM is a tumor specific antigen which is overexpressed in a majority of carcinomas, particularly adenocarcinomas including those of the colon, breast, prostate, liver, lung, head and neck, esophagus and pancreas. EpCAM over expression appears to be associated with enhanced cell proliferation and malignant behaviors potential, as there is a direct link between EpCAM overexpression and cell cycle progression. EpCAM expression was found to be correlated to the histological grading and subtypes in most adenocarcinomas of different sites.Aim: Evaluate the immunohistochemical expression of EpCAM in different grades of MEC and solid variant of adenoid cystic carcinoma (solid AdCC) in comparison with the normal salivary glands, to ascertain the possible prognostic significance and propose EpCAM targeted therapy as a possible treatment approach for patients with salivary gland tumors overexpressing this cell surface marker.Material and Methods: A total of 60 archival paraffin embedded specimens (12 normal salivary gland tissue, 36 MEC and 12 Solid AdCC) were collected and EpCAM expression was evaluated by immunohistochemistry. The total immunoscore (TIS) was evaluated, which represented the product of the proportion score (PS) and the intensity score (IS). The term ‘EpCAM overexpression’ was given for tissues showing a total immunostaining score >4.Results: A highly significant difference was detected between TIS percent values in control, different grades of MEC and solid AdCC. In MEC, EpCAM expression increased in HG-MEC compared to IMG-MEC and LG-MEC (Pearson's chi square test, p < 0.01), but no significant difference was observed between LG-MEC and IMG-MEC (Pearson's chi square test,P> 0.05). Solid AdCC showed the highest TIS percent values in relation to different grades of MEC. HG-MEC and solid AdCC were found to be the highest EpCAM expressors (TIS>4). Although, lack of EpCAM expression was detected in 2 cases (16.7%) of HG-MEC and one case (8.3%) of solid AdCC.Conclusion: EpCAM was frequently detected in MEC and solid AdCC making these tumours potential targets for anti-EpCAM therapies.