Soft tissue tumors are often challenging for pathologists on the basis of morphology alone; therefore, tumor-specific chromosomal aberrations, such as translocations and fusions, amplifications or deletions can be diagnostically useful. Fluorescence in situ hybridization is widely used for the detection of most aberrations in routine diagnostics. Furthermore, reverse transcriptase PCR, sequencing and specific immunohistochemical assays are also applied. Next generation sequencing has already contributed to the identification of hitherto unknown aberrations. Molecular pathology is mainly used in sarcomas to discriminate between different tumor entities. In terms of personalized therapy and targeted treatment, molecular pathology can be utilized to detect predictive markers.