A case of a 66-years-old male with iron deficiency anemia for more than 16 years, refractory to management with iron therapy is reported. Fecal occult blood test done several times was found to be negative. Upper and lower endoscopy revealed no source of bleeding. Capsule enterscopy showed no vascular malformations in the jejunum and ileum. The patient was managed with repeated blood transfusions. Abdominal ultrasound followed by CT scan abdomen revealed right renal soft tissue lesion. A CT-guided biopsy was then taken; the histopathology revealed a clear cell renal cell carcinoma. Right radical nephrectomy was done; the patient's hemoglobin showed a dramatic increase to 14 g/dL within one month. The dramatic response of the anemia to surgery mandates considering renal cell carcinoma in the workup of the possible causes of iron deficiency anemia. Only one similar case has been previously reported.