Bone and soft tissue sarcomas are an infrequent group of tumours. Their prevalence is 4 in 100,000 people/year, making the disease quite rare. Some of these tumours, such as synovial sarcoma, Ewing tumour and osteosarcoma, are more usual in adolescents or in young adults; there are, though, some neoplasias such as leiomyosarcoma or liposarcoma that are more frequent in patients over 55 years. There are more than a hundred different types of sarcomas from the histological point of view. This is the main limitation at the time of finding major clinic essays on patients with specific types of sarcomas. 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 Ewing tumour); 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 describes diverse types of molecular alterations as well, their utility in the clinical domain, as well as implications for the pathologist in translational research in sarcomas.