An analysis is made of current concepts about heterogeneity, instability and autonomy of tumor cells which accounts for the clinical course of incurable, late-stage malignant disease which as such is characterized by a growing independence from growth control mechanisms of the host, by progressive metastatic spread and by unpredictable malignancy associated events. Increasing heterogeneity, instability and autonomy are best demonstrated by the development of resistance phenomena and are potentially reversible processes. This reversibility can be exploited using biological response modifiers. Understanding this triad also helps explain certain clinical phenomena such as qualitative differences in remissions and mixed responses, early vs. late stage disease, and the potential therapeutical hazards which can lead to further tumor heterogeneity. On the breast cancer example further clinical implications are illustrated, namely receptor heterogeneity, autocrine autonomy, and combination therapy with hormones. The concepts discussed are the basis for the development of non-toxic tumor therapies which are aimed less at tumor cell kill than at stabilization.