Recent debate among the experts of cancer research regarding the main causes of carcinogenesis encouraged us to review the etiology of cancer pathogenesis. The somatic mutation theory attributes carcinogenesis to random errors in DNA multiplication while the tissue organization field theory ascribes causation to environmental factors. We recognize complexity in cancer pathogenesis and accept the premise of both DNA multiplication errors and environmental factors in cancer development. Furthermore, it should also be noted that the combination of these factors and the relative importance of the each differ in various types of cancers. For example, in some cancers, genetics plays a prominent role while in others environment such as obesity plays a much stronger role. Additionally, the cancer mitigating factors should also be considered. The balance of cancer-enhancing and cancer-suppressing forces determines the cancer incidence. Ultimately, identifying the lifestyle factors that revise somatic mutations or epigenetic alterations will lead to a clear understanding of pathogenic mechanisms of cancer and to the optimal preventive strategies. This narrative review evaluates the published evidence on carcinogenesis pertaining to the whole organism(thus, holistic) incorporating genetics, epigenetics, immunology, inflammation and infections with emphasis on oral infections. Recent debate among the experts of cancer research regarding the major causes of carcinogenesis led us to review the etiology of cancer cancersgenesis. complexity in cancer pathogenesis and accept the premise of both DNA multiplication errors and environmental factors in cancer development. For example, in some cancers, genetics plays a prominent role while in others environment such as obesity plays a much stronger role. as, the cancer mitigating factors should also be considered. The balance of cancer-enhancing and cancer- , identifying the lifestyle factors that revise s This narrative review evaluates the published evidence on carcinogenesis pertaining to the whole organism (thus, holistic) incorporating genetics, epigenetics, immunology, inflammation. and infections with emphasis on oral infections.