We report a case of primary leiomyosarcoma of the distal femoral shaft arising in a patient who had undergone bilateral orbital enucleation for bilateral retinoblastoma several years previously. Radiography demonstrated an osteolytic, expansive lesion with cortical destruction anteriorly in the distal femoral shaft, and these findings were confirmed on CT. MR imaging revealed an expansive intramedullary lesion with cortical breakthrough and soft tissue extension. The occurrence of a second malignancy in patients with a history of bilateral retinoblastoma is well documented. Many different histological types have been described, with osteosarcoma and leiomyosarcoma occurring with the greatest frequency.