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The main complication of acquired cystic kidney disease (ACKD) is frequent development of renal tumors, including renal cell carcinoma (RCC). Intratumoral deposition of calcium oxalate (CaOx) is a distinct feature of ACKD-associated RCCs, but several features of this type of RCC are not known. Features of the 30 end-stage renal disease (ESRD)-associated RCCs identified within a 13-year period, including eight with CaOx deposition, were analyzed. Pathologic and clinical features of CaOx positive (+) and negative (−) RCCs were evaluated and compared. The CaOx+ RCCs showed higher tendency for bilaterality and multifocality. Seven tumors displayed distinctive morphologic features characterized by tumor cells with ill-defined cell membrane, abundant granular eosinophilic cytoplasm, large nuclei, and prominent nucleoli. One tumor was of clear cell type. Regardless of histologic type, all tumors displayed a proximal tubular differentiation. No significant difference was noted for tumors' stage, proliferation, and apoptosis rate between the CaOx+ and CaOx− RCCs. CaOx+ RCCs account for a significant portion of all ESRD-associated RCCs. The majority of these RCCs display a distinctive morphologic profile. Proximal tubular cell differentiation in conjunction with ESRD-mediated high serum level may be pathogenetically important for intratumoral CaOx deposition. These RCCs seems to have a relatively good prognosis.