An 18-month-old white girl had a malignant melanotic neuroectodermal tumor of infancy of the left femur. Light microscopic findings of a biopsy specimen of the femoral lesion demonstrated the characteristic histologic features, that is, nests of small cells with hyperchromatic nuclei and scant cytoplasm lying within cleftlike spaces lined by cuboidal, melanin-producing cells. Electron microscopy confirmed both neuroblastic and melanocytic differentiation. Despite radiation and chemotherapy, an extensive pelvic tumor developed, which prompted laparotomy 20 months after the femoral biopsy, The apparently metastatic tumor was largely necrotic, but viable nests of undifferentiated small cells and rare individual melanin-containing cells were identified. The patient died 4 months later, at 3 years of age. This case is of particular importance because it is the first example of this tumor found in a long bone. No similar lesions were seen in 17,000 primary tumors of bone treated and seen in consultation at this institution. Its aggressively malignant clinical course is also unusual; only 6 of the 159 cases of melanotic neuroectodermal tumor of infancy reported to date have expressed malignant behavior.