Differential diagnosis of soft tissue sarcomas is so difficult and complex. A healthy functioning of the diagnosis process is possible with strong cooperation. Multidisciplinary tumor councils formed with the participation of physicians who are experts in the field of musculoskeletal tumors have great importance in this regard. Councils provide detailed clinical, imaging and histopathological evaluation. Since the clinical findings of the orthopedic oncologist are guiding for the radiologist and pathologist, they are so valuable and are the first step of the diagnosis process. However, the development of imaging technology in line with the opportunities offered in recent years and many innovations in the field of pathology have offered us new opportunities in differential diagnosis. In recent years, there have been remarkable developments especially in the field of molecular pathology, and researchers have revealed the connection of hundreds of molecules with soft tissue cancers. In this way, molecular methods using techniques such as polymerase chain reaction (PCR), in-situ hybridization (ISH), fluorescent in-situ hybridization (FISH), ribonucleic acid (RNA) sequencing and deoxyribonucleic acid (DNA) sequencing have become complementary to traditional pathology. While these developments enable us to better recognize soft tissue cancers and diagnose them correctly, on the other hand, they have created a wealth of differential diagnosis.