Differentiation among malignant tumors, benign tumors, and normal tissue is highly important in the diagnosis and treatment of many malignancies. We have proposed a dynamic schema for noninvasive characterization of pressure-induced changes in solid tumors. Our hypothesis has been that the altered neovascularization processes within cancer-bearing tissues may significantly increase vascular resistance and cause a much slower response of hemoglobin concentration during a dynamic compression stimulus. This hypothesis was tested by the evaluation of data generated from human tumor clinical testing and from animal tumor model testing. In the human tumor clinical testing, a unified diagnostic criterion was derived that integrated the relative characteristics of tumor oxygen, hemoglobin, and hemoglobin dynamics. By applying such a unified criterion, we were able to differentiate benign breast lesions and malignant breast tumors with high sensitivity and specificity within a subset of 14 suspicious breast lesions with similar size and depth characteristics. In the animal testing, a stepped compression load was applied to the subcutaneous tumor deposit on an athymic NU/NU nude mouse model with subcutaneous xenograft BxPC-3 cancer. Characteristic differences were observed between the premortem tumor and the postmortem tumor in terms of pressure-induced tumor structural and functional changes.