Background: Primary adenocarcinoma of the renal pelvis is an extremely rare type of cancer, accounting for only 1% of all tumors in the urinary tract. Unfortunately, there are no distinct symptoms, imaging characteristics, or established treatments for this condition. These rare tumors can be categorized into three subtypes: (1) Tubulovillous (71.5%)—gland-like structures with villous projections, (2) mucinous (21.5%)—producing excessive mucus, and (3) papillary (7%)—forming finger-like projections. Although their pathogenesis is not well defined, adenocarcinomas are likely to appear from the neoplastic metamorphosis of the glandular cells of the urothelial intestinal metaplasia generally arising in response to habitual prickly stimulants, chronic inflammation, urolithiasis, and hydronephrosis. Case description: A 43-year-old female presented with complaints of left flank pain for 6 months and was diagnosed with left pyelonephrosis with nonfunctioning kidney. She underwent left open simple nephrectomy 4 months ago. The specimen was sent for histopathological examination. Gross examination of the kidney showed a congested external surface, and the cut surface was necrotic and friable with no hemorrhage. The corticomedullary junction could not be identified with a dilated pelvicalyceal system. Microscopic examination showed the presence of tumor cells in an irregular glandular pattern with features of dysplasia. The adjacent renal parenchyma showed the presence of glomerulosclerosis, tubular thyroidization, and marked chronic inflammatory infiltrate within the interstitium. Histopathological findings suggested adenocarcinoma likely of pelvic origin with chronic pyelonephritis. Immunohistochemistry (IHC) markers such as CD20, special AT-rich sequence-binding protein 2 (SATB2), and CDX2 showed positivity, while CK7 and GATA3 were negative, confirming the diagnosis of renal pelvis adenocarcinoma, enteric type. Conclusion: Our case was presumably one of many cases showing contemporaneously every step of carcinogenesis in this rare excrescence, supporting the thesis of cancer progression from the urothelium through metaplasia in an accretive process analogous to colonic carcinogenesis. Clinical significance: Accurate diagnosis of this uncommon neoplasm necessitates postoperative histopathological and immunohistochemical evaluation. Urologists, pathologists, and radiologists must remain vigilant for neoplastic changes in patients with chronic inflammatory conditions or prolonged nephrolithiasis.