A known complication of long-term hemodialysis, acquired cystic kidney disease (ACKD) has been reported infrequently in association with chronic ambulatory peritoneal dialysis (CAPD). The duration of end stage renal failure (ESRF) is thought to correlate with the development of ACKD. Renal cell carcinoma has been reported in 4-10% of patients with ACKD. Two patients on CAPD for more than 6 years without prior hemodialysis treatment developed renal malignancy in the setting of ACKD. Flank and abdominal pain was the presenting symptom in both patients neither of whom had hematuria. Renal ultrasound detected cystic lesions consistent with ACKD; malignant masses were ultimately identified by CT scan. Both patients underwent flank radical nephrectomy, resumed CAPD early in the postoperative period and continue on CAPD 9 and 4 months after surgery. One patient has since developed hepatic metastasis. ACKD is an important risk factor for the development of renal cell carcinoma not only in maintenance hemodialysis patients but also in the CAPD population. A high index of suspicion and serial ultrasound screening for ACKD is warranted in patients with long-term dialysis-dependence.