This lecture introduces the evolving paradigm of Molecular Pathological Epidemiology (MPE) as simply as possible.  Any given human disease represents fundamentally heterogeneous process, as implicated by the "unique disease principle".  MPE dissects complex interplay between environment, lifestyle factors, molecular pathogenic alterations, and disease occurrence and progression, using large populations.  MPE is a logical next step of genome-wide association studies (GWAS), termed “GWAS-MPE Approach”.  MPE has proven itself to be a promising approach to identify biomarkers for precision medicine (Chan A et al. NEJM 2007; Liao X et al. NEJM 2012; Nishihara R et al. NEJM 2013, etc.).  Recently, the "pharmaco-MPE" paradigm (Ogino S et al. npj Prec Oncol 2017) has been utilized to uncover effects of medications on health and diseases.  In addition, the "immuno-MPE" approach integrates immunology and MPE, to decipher effects of environment on immune status in health and diseases.  It is increasingly critical to design large-scale population-based MPE databases worldwide by means of integrating medication use, lifestyle factors, molecular pathology, immune status, and clinical outcome.  Such databases can generate novel information on potential chemopreventive or therapeutic benefits of drugs, which can be further tested by experimental models and clinical trials.  To expand opportunities and address challenges, the "International Molecular Pathological Epidemiology (MPE) Meeting Series" was established in 2013, and the Fourth International MPE Meeting will be held in Boston in 2018 (May 31 to June 1).  Because disease heterogeneity is a ubiquitous phenomenon, the MPE concept should be widespread to advance biomedical and population health sciences in the 21st century, and move us towards precision prevention and treatment.