The applicability of the telomerase reverse transcriptase (TERT) gene Rs2736100 polymorphism in cancer research has been well documented for various malignancies except for head and neck cancers, where data is sparse. This study aimed to analyze this polymorphism with the pathological characterizers of laryngeal squamous cell carcinoma (LSCC) patients. Genetic testing was performed using the Real-time PCR technique on 56 paired samples of biological material (blood and tissue). Data were analyzed using Epi info 7 software. The subjects were predominantly male (95% vs. 5%), with a median age of 62 years, and smokers (89%). The primary tumor origin site was the glottic region (34%), and the advanced clinical stages III-IV were more common (46% vs. 18%). Results show high frequencies for the mutated variants of Rs2736100 (CC 36%>AC 34%>AA 30%), while distribution according to tumor classification criteria leaned towards moderately differentiated carcinoma specimens in T3-T4 stages for the AC/CC variants (P-value without statistical significance) but positively favored the relationship between the AA variant and lack of lymph node metastasis (P=0.0106). The genotypes tend to associate themselves with a better histological presentation regarding the pattern of tumor invasion and, thus, better prognostic values for LSCC. Results suggest that the wild-type genotype of TERT Rs2736100 may be a protective factor for lymph node metastasis and histological pattern of tumor invasion in LSCC. Results regarding the synergistic relationship between cancer and smoking corroborate literature data for moderate to severe smokers regardless of the genetic variant.