To understand the underlying mechanisms of differences in patterns of tumor-specific hypermethylation, we have analyzed the aberrant promoter methylation profile of HNSCC using seven important tumor-related pathway genes, including DAPK, RASSF1 (apoptosis pathway), BRCA1, MLH1 (DNA repair pathway), p16 (cell-cycle pathway), ECAD (cell-cell adhesion), GSTP1 (Xenobiotic pathway) and three methylated loci (MINT1, MINT2 and MINT31) in the high cancer incidence zone of Northeast India. The gene discussed is MLH1; the disease is head and neck squamous cell carcinoma.