This article reports a challenging case of severe urinary tract infection accompanied by lymphadenopathy. The patient was admitted with a chief complaint of "cloudy urine for over four months." Imaging revealed thickening of the left ureteral wall with severe hydronephrosis of the left kidney. PET/CT demonstrated multiple metabolically active foci in the left kidney, ureter, and bladder, along with metabolically active lymph nodes in the left renal hilum and para-aortic region (SUV_max 9.8), making it difficult to differentiate between metastatic and inflammatory lymph nodes. Four urine cytology tests failed to detect cancer cells. Upon the multidisciplinary consultation on difficult cases in Guangdong Urological Association, consultation, the patient underwent laparoscopic left nephroureterectomy with para-aortic lymph node biopsy. Postoperative pathology confirmed left pyonephrosis and nephrolithiasis, ruling out malignancy. This article discusses the differential diagnostic strategies for distinguishing between lymph node metastasis from urothelial carcinoma and inflammatory lymphadenopathy.