As a result of a compromised and anisotropic microcirculation, isotransplanted mammary tumors in mice exhibit hypoxic and anoxic tissue areas which are heterogeneously distributed within the tumor mass. Similarly, in poorly perfused human breast cancer xenografts, hypoxia develops at early growth stages and expands with tumor growth. In contrast, breast cancer xenografts with high perfusion rates exhibit an oxygenation status comparable to that of most normal organs. There is clear experimental evidence that the efficiency of tumor blood flow in isotransplanted tumors and in xenografted human breast cancers is the principal modulator of tissue oxygenation. The pO2 distribution found in primary lesions in patients ranged from the pO2 histograms obtained in "low-flow" isotransplants and xenografts to those measured in "high-flow" breast cancer xenografts or normal tissues. From our extended and systematic clinical studies there is clear indication that the oxygenation status of human breast cancers in situ does not correlate with the clinical stage and/or histological grade of an individual tumor.