While it is often characterized as a genomically unstable bone sarcoma, no recurrent gene translocation and fusion genes has ever been reported in human osteosarcoma, except for one report which revealed exon 6 of the cAMP-responsive element binding protein 3-like 1 gene (CREB3L1) fused in-frame to the EWSR1 exon 11 in a case of small cell osteosarcoma [23].The most important discovery of the present study is the detection of two recurrent fusion genes, LRP1-SNRNP25 and KCNMB4-CCND3, which are validated by RT-PCR, Sanger sequencing and FISH. The gene discussed is CREB3L1; the disease is osteosarcoma.