Alpha-fetoprotein (AFP) is a common tumoral marker in pediatric neoplasms; increased serum levels are usually encountered in tumors arising from tissues producing AFP during fetal life. However, elevation of such protein is rarely found in patients with Wilms tumor (WT). Three patients with WT and elevated serum AFP were studied over the course of the disease. One patient had left WT with invasion of aorto-caval lymph nodes and lung metastases. The second patient was referred to our center for abdominal recurrence of bilateral WT whereas the third showed right WT with inferior vena cava thrombosis. AFP levels demonstrated a trend parallel to decrease/increase of tumor size, with further elevation in patients with metastases. Elevated AFP serum levels in patients with WT could be related to peculiar histological features and serial dosage might be a useful diagnostic and prognostic test.