Soft tissue sarcomas constitute a heterogeneous category of neoplasms composed mostly of uncommon tumours of different histology, different biology, and different outcome. Thirty years ago, the diagnosis of these neoplasms was mainly based on morphology coupled with some classical histochemical stains such as periodic acid-Schiff, reticulin, and trichrome stains. In the last 15 years, thanks to the substantial development of immunohistochemistry, cytogenetics and molecular genetic analysis significant improvements have been made regarding the classification and diagnosis of these tumors, with direct implications for clinical management and prognosis [1, 2]. Many new entities were recognized of which desmoplastic small round cell tumor and intimal sarcomas are examples. Other sarcoma entities gradually disappeared or lost in importance (e.g., the so-called malignant fibrous histiocytoma [3], hemangiopericytoma [4], and fibrosarcoma categories). During the same period of time, molecular ancillary techniques (including a vast array of polymerase chain reaction-based techniques, fluorescence in situ hybridization (FISH), conventional and array-based comparative genomic hybridization, expression arrays, direct genome sequencing, and DNA methylation analysis to name a few) allowed detailed analysis of these tumors and the resulting data facilitated better understanding of their biology (Fig. 1). In addition, thanks to improvements in nucleic acid preservation and isolation, many molecular techniques provided new parameters important for diagnostics and/or prognosis and were modified to be applicable on formalin-fixed, paraffin-embedded material (e.g., FISH, polymerase chain reaction-based techniques). This is all condensed in a substantial revision of the World Health Organization classification which combined histology with genetics [2]. Methodological advances thus allowed better understanding of biology, within turn novel classifications based upon new histogenetic concepts and robust diagnostic methods.