Humoral hypercalcemia can arise from a variety of malignancies, but its association with primary colorectal carcinoma is rare, with only 20 such cases documented in the English-language literature to date. We report an additional case to clarify the clinicopathologic features of colorectal carcinoma with humoral hypercalcemia. A 54-year-old woman was admitted with symptomatic hypercalcemia of 14.2 mg/dl and multiple hepatic metastases, 2 years after resection of sigmoid colon cancer. The hypercalcemia was caused by the circulating parathyroid hormone-related peptide (PTHrP) produced by poorly differentiated adenocarcinoma in the liver. The PTHrP level on admission was 13.5 pmol/l. Despite systemic chemotherapy, the patient died of disease progression 3 weeks after the humoral hypercalcemia was diagnosed. A review of the 21 reported cases, including ours, suggests that colorectal carcinoma associated with humoral hypercalcemia is characterized by a poorly differentiated tumor with or without squamous or neuroendocrine features, distant metastases, and a dismal prognosis.