Hypercalcemia is a well-known manifestation of paraneoplastic syndromes associated with a variety of malignancies. However, colon cancer has only rarely been associated with hypercalcemia. Here we present the first case of adenosquamous carcinoma of the sigmoid colon in a patient who was found to have hypercalcemia associated with parathyroid hormone-related protein (PTHrP), with no radiological evidence of metastasis to other organs. A 78-year-old woman was admitted to our hospital complaining of lower abdominal pain. Physical examination and computed tomography revealed a tumor, 13 cm in diameter, in the sigmoid colon. Laboratory data showed an elevated serum calcium level (11.2 mg/dl). Primary colostomy was performed. After the primary operation, the patient was found to have hypercalcemia and an elevated PTHrP level. We performed sigmoidectomy, total hysterectomy, and partial urinary bladder resection 1 month after the primary operation, and both PTHrP and calcium levels immediately returned to normal. The histopathologic diagnosis was poorly differentiated adenosquamous carcinoma. The patient died due to tumor recurrence 4 months after the second surgery.