Sarcomas account for less than 10% of all human malignancies that are believed 
to originate from as yet poorly defined mesenchymal progenitor cells. They 
constitute some of the most aggressive adult and childhood cancers in that they 
have a high metastatic proclivity and are typically refractory to conventional 
chemo- and radiation therapy. Ewing's sarcoma is a member of Ewing's family 
tumors (ESFT) and the second most common solid bone and soft tissue malignancy 
of children and young adults. It is associated in 85% of cases with the 
t(11;22)(q24:q12) chromosomal translocation that generates fusion of the 5' 
segment of the EWS gene with the 3' segment of the ETS family gene FLI-1. The 
resulting EWS-FLI-1 fusion protein is believed to behave as an aberrant 
transcriptional activator that contributes to ESFT development by altering the 
expression of its target genes in a permissive cellular environment. Although 
ESFTs are among the best studied sarcomas, the mechanisms involved in 
EWS-FLI-1-induced transformation require further elucidation and the primary 
cells from which ESFTs originate need to be identified. This review will 
highlight some of the most recent discoveries in the field of Ewing sarcoma 
biology and origins.