Bone and soft tissue sarcomas are an infrequent group of tumours with a prevalence of 4 in 100000 people/ year. Sarcomas, such as synovial sarcoma, Ewings sarcoma and osteosarcoma, are more usual in adolescents or in young adults. Neoplasias such as leiomyosarcoma or liposarcoma are more frequent in patients over 55 years. One relevant topic is related to sarcomagenesis elucidation, a key for discovering the early molecular mechanisms involved in the development of sarcomas as well as the identification of reliable molecular markers and possible therapeutic targets. Today, it is known that the cellular context contributes to the phenotype. Analysis of gene expression profiling of human sarcomas revealed tightly clustered groups and could denote the existence of common signalling pathways for each branch. From the molecular point of view, these neoplasias are grouped into two main types: (a) sarcomas showing specific genetic alterations and relatively simple karyotypes, and translocations which originate gene fusions (e.g., EWS-FLI1 in Ewings sarcoma); or specific genetic mutations (e.g., c-kit in the gastrointestinal stromal tumour), and (b) sarcomas showing unspecific gene alterations and very complex karyotypes, and very numerous gains and losses. This review points out the clinical projection of sarcomagenesis elucidation and knowledge of diverse types of molecular alterations.