We present a case of transitional cell carcinoma (TCC) of the renal pelvis in a patient with autosomal dominant polycystic kidney disease (ADPKD) who presented with hypercalcemia. Hypercalcemia is rare in TCC and has not been independently associated with ADPKD. Preoperative magnetic resonance imaging findings suggested a diagnosis of TCC. The patient underwent left nephroureterectomy, which confirmed the diagnosis, and received adjuvant chemotherapy. The hypercalcemia had not recurred, and she was without evidence of disease recurrence at 36 months. This case is unique in that we did not find any previously reported cases of TCC associated with ADPKD and hypercalcemia.