Soft tissue sarcomas represent a heterogeneous group or rare mesenchymal malignancies, with an annual incidence of approximately 5 cases/100.000. Bone sarcomas are even rarer, with an incidence around 0.3/100.000/year. Median age of incidence of soft tissue sarcomas is around 60 years, but is related to histology (i.e., rhabdomyosarcoma and Ewing’s sarcoma occur in children and young adults, whereas pleomorphic sarcomas affect adults and elderlies). Main sites of occurrence also depend on histology. Overall, the lower limbs, followed by the upper limbs, the trunk, and the head & neck region, represent the most frequently affected anatomic locations. Some anatomic sites are related to specific histologies, such as the retroperitoneum, for well differentiated/dedifferentiated liposarcoma and leiomyosarcoma. Visceral locations are quite rare, with the exception of uterine leiomyosarcomas, with an incidence of approximately 0.5/100,000/year, but soft tissue sarcomas may occur at any visceral site. Diagnosis is based on a combination of classic microscopic morphology, immunophenotype and molecular genetics. The current WHO classification of bone and soft tissue sarcomas recognizes more than 80 distinctive malignant histologies. Accurate classification of mesenchymal neoplasms traditionally represents a major diagnostic challenge. Published data demonstrate that approximately 30% of sarcomas are subjected to inaccurate classification. Main reasons are represented by the intrinsic diagnostic difficulty of this subset of cancer but also by their rarity. This situation intuitively affects both the achievement of the necessary expertise and the efficacy of educational efforts. The accurate recognition of the many histologic subtypes currently represents a main step to proper therapeutic planning. In the past, diagnostic accuracy was perhaps less crucial when treatment options were limited. By contrast, recent therapeutic advances have made proper sarcoma classification mandatory, also in regard to subtyping within the family of soft tissue sarcomas. The creation of collaborative networks as well an extended use of expert second opinion is therefore strongly advised.