Objectives. Patients presenting with head and neck cancer may have no clinical or radiological evidence of cervical lymph node metastasis – the N0 neck. Despite this, histo-pathological data has confirmed the presence of occult metastases in up to 30% of N0 necks (i.e. N+), depending on the site of the primary tumour. Currently there is no way of identifying affected individuals and consequently, 70% may be overtreated.1 Using proteomic and immuno-histochemical (IHC) techniques, we attempted to identify a primary tumour phenotype, which would allow the discrimination of laryngeal squamous cell carcinoma (LSCC) with metastatic potential. Method. Six fresh frozen primary LSCC samples; three each from patients with a histopathologically confirmed N+ or N0 neck were used. Following homogenisation of the tumour tissue, protein separation using 2D gel electrophoresis was performed. Differences in individual protein expression between N0 and N+ groups were identified using Progenesis SameSpots® gel analysis software. Differentially expressed proteins were extracted from the gels and identification was achieved using a combination of matrix-assisted laser desorption and ionization mass spectrometry (MS) (MALDI) and liquid chromatography tandem MS (LC-MS/MS). Results. Ten strongly differentially expressed proteins were identified. Those identified included heat shock protein 90, T complex protein 1 gamma, Bromodomain PHD finger protein 3 and lactate dehyrogenase A, which were up-regulated and thymidine phosphorylase which was down-regulated in N+ samples. Conclusions. These proteins represent potential biomarkers of metastatic potential in LSCC. Further investigation of their worth as biomarkers is necessary using, in the first instance, large sample tissue microarrays. Reference. 1 Yarbrough W.G., Slebos R.J.C. & Liebler D. (2006) Proteomics: clinical applications for head and neck squamous cell carcinoma. Head Neck. 28, 549–558