The proteomic profiles of bone and soft tissue sarcomas remain largely unexplored. The “proteome” represents all protein isoforms expressed within a target tissue, including those with post-translational modifications. We are using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and liquid chromatography/tandem mass spectrometry (LC-MS/MS) to evaluate proteomic differences between selected sarcomas and their presumed benign counterparts and/or normal tissues. The specific aim of this proposal is to identify sarcoma-specific differences in protein expression that define the malignant phenotype. These findings may elucidate important mechanisms in sarcoma development and lead to novel diagnostic and therapeutic strategies.