Antibody microarrays, two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (2-DE/MALDI-TOF-MS) were used to examine protein changes in 56 oral cancers (OCs)/normal controls (NCs) from Sudanese (41 OCs vs. 31 NCs) and Sri Lankan (15 OCs vs. 15 NCs) patients. Pools of extracted proteins were prepared and used for microarrays/2-DE/MALDI-TOF-MS. From 2-DE, protein spots (differentially-expressed) were cut and identified with peptide mass fingerprinting based on MALDI-TOF-MS, and the proteins were identified by submitting peptide mass profiles to the NCBInr database. By microarrays, 6 and 8 proteins demonstrated significant differences in their abundance values as differentially-expressed in OCs examined from Sudan and Sri Lanka, respectively. For some of the proteins found, like p56dok2 and NEK2, this is the first report in OCs. By MALDI-TOF-MS/2-DE, patterns of OCs/NCs were acquired and tumour-associated proteins, like psoriasin, calgranulin-B and glutathione transferase, were found to be altered in OCs compared to NCs. The proteins found in this work (by two different methods) represent a global protein change specific to OCs from two populations. This might indicates involvement of multiple pathways in the process of tumorgenesis; thus, multiple proteins should be simultaneously targeted in OCs. The finding of few common proteins might suggest involvement of different pathways, which may parallel differences in ethnicity and/or lifestyle.