Diagnosis of renal cell carcinoma (RCC) in patients with autosomal dominant polycystic kidney disease (ADPKD) is challenging and often delayed due to accompanying multiple renal cysts. Sometimes, it is difficult to distinguish RCC from cyst infection or hemorrhage. We herein present the case of a patient with ADPKD undergoing long-term hemodialysis whose sarcomatoid RCC was difficult to diagnose and was confirmed via nephrectomy. A 53-year-old male, undergoing hemodialysis since 20 years for end-stage renal disease secondary to ADPKD, was admitted to our hospital with a 3-week history of fever at > 38 °C and right flank pain. Clinical manifestations were compatible with cyst infection. Magnetic resonance images of the lesion identified in the lower right kidney, revealing slightly high signal intensity on T1-weighted images, low signal intensity on T2 weighted images, and restricted diffusion on diffusion-weighted images, were also consistent with those of cyst infection. Therefore, antibiotic therapy with ciprofloxacin, doripenem, and vancomycin was initiated. However, the patient's symptoms did not improve. Consequently, right nephrectomy was performed for both diagnosis and treatment, which revealed a sarcomatoid RCC with metastasis to the regional lymph node. The patient gradually developed cachexia and died on day 106 post-admission. The present case illustrates the difficulty of diagnosing RCC in patients with ADPKD, particularly sarcomatoid RCC, which is a rare and aggressive variant of RCC, even with the use of various types of imaging modalities. An early decision of nephrectomy may be necessary in such cases.