A 42-year-old woman visited the emergency room for pain in her right lower abdominal quadrant. Abdominopelvic computerized tomography (CT) revealed postrenal obstructive hydronephrosis without a definitive mass in the upper urinary tract [Figure 1a], which suggested renal/ureteral tuberculosis or an unknown masked metastatic carcinoma. Positron emission tomography/CT revealed multiple high-intensity signals in the C7 to T4 spinal vertebrae and intra-abdominal para-aortic lymph nodes, suggesting metastatic malignancy of unknown origin (MUO) [Figure 1b]. Examination of a cytological preparation from a urine specimen found clusters of large atypical cells with abundant cytoplasm and prominent nucleoli, suggesting malignancy, type undetermined [Figure 2a]. Subsequent double immunostaining for CK20/P53 expression of a cytological preparation from the same urine sample found CK20-positive umbrella cells [Figure 2b] and CK20-positive/p53-positive atypical cells, suggestive of UC [Figure 2c]. Systemic review was unable to identify definitive evidence of a metastatic primary malignancy that caused ureteral obstruction. The patient underwent right nephroureterectomy for the definitive diagnosis and treatment. The operative findings included an ill-defined infiltrating mass (2.5 cm) in the lower right renal pelvis [Figure 3a]. Histopathological examination found tumor cells that were arranged in micropapillary clusters with frequent lymphovascular invasion [Figure 3b]. The tumor cells infiltrated through the renal parenchyma into perinephric fat tissue, indicating advanced disease (pT4) [Figure 3c]. Diffuse in situ UC was found in the associated ureter. The patient has been stable over 3-month observation period after two cycles of adjuvant chemotherapy.