We report the case of a 34 year old male presenting with symptomatic hypercalcemia due to excessive PTHrP secretion from a pancreatic neuroendocrine carcinoma with extensive hypervascularization and without any evidence for metastatic disease. In the early phase of the disease conventional chemotherapy with streptozocin and doxorubicin was able to control functional activity as well as tumor growth. However, after 2 years tumor escape was indicated by severe therapy-resistant hypercalcemia. Therapeutic options were reduced due to the excessive tumor vascularization and the patient died from his disease after a short period of intensified therapy. The role of PTHrP in hypercalcemia of malignancy (HHM) and its association with neuroendocrine pancreatic tumors as well as possible therapeutic options are reviewed.