An 8-year-old spayed female domestic ferret (Mustela putorius furo) was presented for evaluation of anal prolapse and bilateral enlarged anal sacs. A lobulated mass in the right perianal area was detected during the physical examination. Results of diagnostic blood testing confirmed decreased glucose, potassium, and phosphorus concentrations, and increased total and ionized calcium concentrations. Complete resection of the mass was not possible owing to its nearness to the rectum and the ventral aspect of the tail. Imprint cytological preparations obtained intraoperatively were compatible with anal sac adenocarcinoma, which was confirmed by histopathologic evaluation of submitted tissue samples of the mass. Routine staging showed iliac lymph node and presumptive lung metastases; therefore, chemotherapy was initiated. This report describes a confirmed case of anal sac adenocarcinoma with metastases and hypercalcemia, managed with surgery and chemotherapy for 13 months after the patient's initial presentation and diagnosis.