Abstract: Mutual alternative pathways of influence central to neoplastic disease development and progression appear based on a multiplicity of associated genetic lesions that are generated and expressed via common pathways of effective influence. Indeed, an integral participation of the organism would paradoxically account for central attributes of a selective vulnerability of cells to such environmental factors as hypoxia or carcinogenesis in a manner that reflects an integral genomic participation in such multiplicity of genetic lesion creation and expression in disease. Indeed, a strictly non-Mendelian series of susceptibility traits of an integral genome might help account for development of a neoplastic lesion in a given individual that integrally evolves both in terms of creation of further multiple genetic lesions in the involved genome and also in terms of subsequent expression of such created multiple genetic lesions in this given integral genome. In simple terms, a given neoplastic lesion that is generated and that progresses in a focal region of a given organ or tissue would paradoxically belie a multiplicity in predisposition to a combined creation and expression of genetic lesions within an integral genome of that individual patient. Such paradoxical aspects of neogenesis might help account for a participation of various genetic systems of influence that would associate in terms of pathways that allow the development of a neoplasm that proliferates and spreads only with reference to a contextual involvement of multiple genetic lesions and multiple gene expression of mutations, deletions, or translocations. In such terms, diseases ranging from neoplasms, atherosclerosis, diabetes mellitus, Alzheimer`s disease, even schizophrenia and myocardial infarction, would perhaps evolve strictly as developmental systems of participation of essentially multiple genetic influences that are generated specifically within the integral context of one given genome of an individual.