Heterogeneities exist in endothelial cells and microvascular architecture during tumor angiogenesis. We found significantly variable expression profiles of EC markers, including ephrinB2 and its receptor EphB4, and various types of the architecture. We propose a new concept of tumor microvascular architecture phenotype (T-MAP), reflecting the density, morphology, structure and the three-dimensional distribution of newly formed vessels. The pattern of T-MAP may represent the invasiveness of the tumor therefore predict the outcome of therapy. The presence of T-MAP heterogeneity (T-MAPH) may be utilized as additional diagnostic criteria and for therapeutic designs for antiangiogenesis.