Methylation is one of the fundamental mechanisms of biotransformation reactions followed in nature that can modify the structure and functions of biomolecules. The nicotinamide N-methyltransferase (NNMT) is a human methyltransferase that produces 1-methylnicotinamide (1-MNA) from nicotinamide (NA) by utilizing the methyl group from S-adenosyl methionine (SAM). The upregulated NNMT based endogenous product 1-MNA is projected as a novel biomarker for cancer and also linked with tumor aggressiveness in various forms cancers through epigenetic reprogramming. In the present work, a systematic exploration on the selective methylation of NA to yield 1-MNA rather than 7-MNA is carried out employing computational quantum chemical calculations and by assessing their thermodynamic and kinetic parameters. The present theoretical study also indicates the potential of 1-MNA as a biomarker over 7-MNA in cancer. © 2020 Elsevier B.V.