OBJECTIVE At present, 35% to 50% of patients with clinically localized renal cell carcinoma (RCC) unpredictably have a recurrence after surgical therapy. Presently, no clinical serum marker exists to detect occult metastases and to allow measurement of response to therapy in RCC. Serum ferritin was previously reported to correlate with pathologic stage. We postulated that this increase in serum ferritin with increasing stage might reflect tumor volume, since higher stage tumors are often larger. METHODS Serum ferritin levels were measured preoperatively in 30 patients with radiologic evidence of RCC. Tumor volume and the largest tumor dimension were calculated from either the pathologic specimen (n = 24) or from the computed tomography or magnetic resonance imaging (n = 30). Pathologic stage was determined for all patients undergoing surgery (T1 = 3, T2 = 12, and T3 = 9). RESULTS Preoperative serum ferritin levels did not correlate with age, blood urea nitrogen levels, creatinine levels, hematocrit, race, or gender. Although mean serum ferritin levels increased with increasing stage (T1 = 113 +/- 75, T2 = 254 +/- 270, and T3 = 425 +/- 257 ng/mL), these differences did not reach statistical significance (P > 0.05). Serum ferritin did, however, correlate with tumor volume (R = 0.75; P < 0.0001) and the largest tumor dimension measured from radiographic studies (R = 0.8; P < 0.0001). Serum ferritin measured intraoperatively from the renal vein (666 ng/mL) and the inferior vena cava (564 ng/mL) from a patient with a 500 cc tumor (preoperative serum ferritin, 552 ng/mL) suggested that the tumor was the source of the elevated ferritin levels. Histologic sections from tumors taken from patients with high serum ferritin levels were more necrotic and stained intensely positively for iron and immunohistochemically for ferritin, whereas adjacent histologically normal tissue did not. CONCLUSIONS These data suggest that ferritin may be a useful serum marker for monitoring patients with RCC, but the actual source of the ferritin remains unclear and dictates further investigation.