Sarcomas are malignant soft tissue tumors, accounting for 1% of adult tumors and 8% of all pediatric malignancies. Sarcomas are rare, and display a variety of histological subtypes and clinical characteristics. Therefore, everyday management is difficult in terms of diagnosis,prognosis and treatment. Recently, the development of pangenomic molecular techniquesimproved the clinical management of sarcomas, but the use of microRNAs as biomarkers is still being investigated.In the present work, we studied the value of microRNA expression profiles inrhabdomyosarcomas and osteosarcomas. Raw data of expression profiles were obtained using amedium throughput technology based on quantitative PCR. We first developed an analysismethodology to gain accurate, reproducible and relevant expression data, starting fromheterogeneous samples. Furthermore, we showed that microRNA expression profiles canimprove the clinical management of both sarcoma entities: they are helpful to upgrade the fine nosological classification of rhabdomyosarcomas, and they are able to predict the response of osteosarcomas to neoadjuvant chemotherapy. Searching for new clinical applications tomicroRNA expression profiles must be pursued.