Metabolic changes in head and neck carcinogenesis are often non-specifically correlated with carcinomas. The study of metabolic disorders can improve the understanding of tumourigenesis at the cellular level. This study was designed to evaluate the role of serum homocysteine, folate, and vitamin B levels in the pathogenesis of laryngeal squamous cell cancer (LSCC) by measuring serum levels in 60 consecutive untreated patients with LSCC and 60 controls (30 smokers and 30 non-smokers). Compared with smoker and non-smoker control groups, significantly lower levels of vitamin B-12 were found in patients with LSCC. Folate levels in patients with LSCC were also significantly lower than in the smoker and non-smoker control groups. There were no significant differences in the homocysteine levels between these three groups. Metabolic alterations in vitamin B-12 and folate levels, particularly hypofolataemia, could be associated with the development of LSCC, although further research is required to confirm their roles definitively.