This review reports the main gene signature specific for the diagnosis, prognosis or prediction of drug response in sarcomas. Almost half of sarcomas show a simple genetic lesion which is specific for the diagnosis: recurrent translocations in 10 to 15% of sarcomas, specific activating and inactivating mutations in GIST and rhabdoid tumor respectively, and MDM2 amplification in well-differentiated and dedifferentiated liposarcomas as well as in intimal sarcoma. A recent study reported a gene expression signature which is much better than histological grading for predicting metastasis outcome. This signature is composed of 67 genes all belonging to pathways involved in chromosome integrity suggesting an important role of these mechanisms in the development of metastases. On the other hand, and except for GIST with KIT and PDGFRA mutations, there is no validated predictive gene signature so far.