The rapid development of an osteosarcoma, after surgical resection of an osteochondroma, has not been yet reported. We present here the case of a 12-year-old girl that had, in less than 2 months, an osteosarcoma at the initial site of a treated osteochondroma. Comparative Genomic Hybridization analyses showed that the 2 tumors were genetically distinct, suggesting a distant, if any, relationship. The possible implication of a deregulated tissue homeostasis caused by the surgical intervention is discussed. Proangiogenic factors involved in the tissue healing could be the triggering factor favoring tumor angiogenesis and explaining the very rapid progression of the tumor.