Tumor vascular markers (TVMs) are proteins that are expressed uniquely on tumor vessels. Surprisingly, each tumor appears to have a unique TVM expression pattern. These TVMs represent new targets for antibody therapeutics. Unfortunately, development of anti-TVM antibody therapeutics has been restricted by the lack of animal model system expressing human tumor vessels. Previous studies have used human embryonic stem cells (ESC) to generate tumors with human vessels. It remained undetermined if these vessels were normal vessels or tumor vessels, expressing human TVMs. We therefore tested tumors generated in this model for the expression of TVMs. We tested ovarian and breast TVM expression using ovarian cancer and breast cancer cells in the ESC tumor model. As controls we used tumor cells grown in culture and tumors cells grown in the absence of ESC. RT-PCR analysis confirmed expression of ovarian TVMs in the ovarian/ESC model and breast TVMs in the breast/ESC model. Perhaps not surprisingly, consistent with the developmental nature of the TVMs, the multipotent ESC teratomas also expressed all TVMs. We therefore performed immunofluorescence (IF) and immunohistochemical (IHC) analysis to determine if TVM expression was localized to tumor vessels. In order to distinguish the cancer cells from ESC derived cells, tumor cells were labeled with DsRed. IF analysis confirmed the expression of human vessels in a peritumoral location. In the ovarian tumor model, IHC analysis confirmed vascular expression of several ovarian TVMs, including F2RL1, GPR105, Thy1, β3 integrin, β5 integrin and Tem7. Similarly, in the breast cancer/ESC model vascular localization was confirmed for breast cancer TVMs Jak3 and HoxB2. In order to determine if TVM induction was specific to the cancer cells, we sought to determine if ovarian TVMs were expressed in breast/ESC. IHC analysis demonstrates an absence of expression of the ovarian TVMs GPR105 and F2RL1 in breast/ESC. In contrast, the breast TVMs Jak3 and HoxB2 were not expressed in the ovarian/ESC. Interestingly, we did observe some vascular expression of the breast TVMs SMPD3 and SLITRK6 in the ovarian/ESC model. This suggests that some, but not all TVMs may be induced in a tumor specific manner. Finally we tested this model to evaluate the effectiveness of therapeutics targeting human tumor vasculature. We coupled the saporin toxin to an antibody targeting the TVM Thy1. When anti-Thy1-saporin antibodies were delivered to ovarian cancer/ESC tumors we observed a significant reduction in central tumor viability in vivo; the region dependent on human vasculature. Evaluation of tumors treated with Anti-Thy1-saporin antibodies demonstrated a significant reduction in human tumor vessels relative to controls. These studies confirm the vascular expression of human TVMs in the tumor cell/ESC model. Vascular TVM expression of most TVMs appears to be induced in a tumor specific manner, suggesting that tumor cells may play an important role in the inductions of TVMs. Finally, this model is a useful tool for testing the efficacy of human TVM specific therapeutics in vivo.