Neurofibromatosis may be associated with ossifying subperiosteal hematoma resulting in lower extremity hypertrophy. We presented two girls, aged 10 and 13 years, with neurofibromatosis type 1, who exhibited increased thigh girth on the right side. Plain radiographs showed an ossifying cystic formation. Magnetic resonance scans demonstrated a fluid-fluid level. Diagnosis of ossifying subperiosteal hematoma was confirmed with a biopsy in both cases. In the older patient, radiologic studies after 1.5 years showed an increase in the wall thickness of the femoral cyst from 3 mm to 5 mm. In the other patient, cystic formation surrounding the tibia became more prominent at the end of five years. This patient died from multiple lung metastases following chemotherapy and wide resection for Ewing's sarcoma that developed in the right shoulder.