It is sometimes difficult to make an unequivocal diagnosis of tumours of bone and soft tissue based upon classical morphology alone, which has led to an increased use of additional diagnostic tools. In the past decade new techniques have become available, based on tumour specific genetic alterations, for instance chromosomal translocations. With the cloning of the translocation breakpoints and the identification of the genes involved, the reverse transcriptase polymerase chain reaction (RT-PCR) detection of the fusion gene has become an important diagnostic test. Also, non-tumour specific genetic alterations with prognostic value can be detected.