Background: laryngeal carcinoma is the most common head and neck cancer, with a high rate of metastasis and poor prognosis. It has a global incidence of 3.2 cases per 100,000 and a death rate of 1.1 per 100,000 per annum. Squamous cell carcinomas constitute more than 95% of primary cancer larynx. Despite of the recent advances in the treatment modalities for laryngeal carcinoma, the survival rate of patients with this malignancy has not improved significantly. Therefore, there is an urgent need to identify novel biomarkers for the prediction of tumour progression and metastasis. Epithelial-mesenchymal transition (EMT) process promotes the aggressive behaviour of cancer through downregulation of epithelial markers and upregulation of mesenchymal markers of cancer cells in order to become motile and invasive. Several transcription factors are key regulators of EMT, including the Snail/Slug family, Twist, ZEB1 and ZEB2. Aim of the work: this study aimed to evaluate the immunohistochemical (IHC) expression of the transcription factor Slug as an inducer of EMT and E-cadherin as an epithelial protein in 50 Egyptian cases of laryngeal squamous cell carcinoma (LSCC) and investigation of the relationship between both markers and the clinicopathologic parameters. Material and Method: the material of this study included 50 specimens of LSCC. All specimens were embedded in paraffin and stained with Hematoxilin and Eosin (H & E) for histopathological evaluation. Other Sections were immunostained with antibodies to Slug and E-Cadherin. The results were tabled, statistically analyzed and discussed. Results: high tumor grade and high TNM stage were positively correlated with Slug IHC expression (P-value= 0.02 and 0.001) but inversely correlated with E-cadherin IHC expression (pvalue= 0.006 and 0.03) respectively. Conclusion: LSCC patients with Slug IHC overexpression and reduced Ecadherin IHC expression are at higher risk of metastatic carcinoma and might benefit from more aggressive treatment after surgery.