In terms of essential mechanics of development of the malignant phenotype, systems of evolutionary-type progression might specifically relate to chromatin-remodeling disturbances as a basic framework in inducing states of self progressive genetic instability. In view of the subsequent accompanying features involving progressive dedifferentiation and high mitotic activity, neoplastic lesions might paradoxically evolve as specific systems of interaction with a stroma of fibroblastic participation towards further enhanced genetic instability. Indeed, in a real sense, mutagenesis of tumor cells would appear to involve active participation of a stroma that both maintains and further induces increasing mutagenesis in terms of an increased mitotic activity of the tumor cells. In addition, apoptosis and necrosis of neoplastic tissue would themselves arise and evolve as additional mechanistic effects of such increased mitotic activity together with evolving genetic instability. Indeed, in simple terms, perhaps, systems of disturbed chromosomal segregation and of spindle disruption together with disturbed cell cycle checkpoint dynamics would account for both genetic instability and mutagenesis in a context of increasing mitotic activity involving also stromal participation towards infiltrative growth and spread of the neoplasm.