A 60-year-old woman was diagnosed with esophageal small cell carcinoma in October 2004 and received chemotherapy. However, the tumor grew gradually and multiple bone metastases occurred. Anorexia, nausea, emesis, numbness in both hands, and disturbed consciousness developed at the end of January 2006, and the patient was admitted to Fukushima Medical University Hospital. Abdominal pain, marked hypercalcemia and hyperamylasemia were noted and the patient was diagnosed with severe acute pancreatitis. Because the level of blood parathyroid hormone-related protein was elevated, we considered that esophageal small cell carcinoma caused human hypercalcemia of malignancy and that metastatic bone tumors caused local osteolytic hypercalcemia, eventually leading to severe acute pancreatitis. This is an extremely rare case of esophageal small cell carcinoma associated with hypercalcemia causing severe acute pancreatitis.