Laser Microdissection (LMD) associated to LC-MS/MS were used to analyze the proteome of neoplastic islands and stroma tumor of Formalin-Fixed and Paraffin Embedded (FFPE) OSCC tissues to identify proteins of prognostic value. Label-free protein quantification and statistical analysis revealed neoplastic islands proteins and from stroma tumor as correlated to clinicopathological data including lymphonode status and recurrence.