Considerable evidence indicates that serotonergic mechanisms, particularly the serotonin transporter, are involved in alcoholism and tobacco use and are influenced by polymorphism of the promoter region of 5HTT (5-HTTLPR). As alcohol and tobacco consumption have been implicated in the pathogenesis of oral cancer, the purpose of this study was to investigate 5-HTTLPR polymorphism in patients with oral squamous cell carcinoma (OSCC) compared with a control group in a sample of Brazilian patients. One hundred and three patients affected by OSCC and 103 volunteers without OSCC were genotyped for 5-HTTLPR. Both groups were matched for age, sex and tobacco use. The chi-squared test was used for statistical analysis (α=0.05). There was no statistically significant difference in 5-HTTLPR genotypes between case and control group (p= 0.408). In conclusion, the present investigation demonstrated that serotonin transporter polymorphisms are not implicated in the OSSC development.