Vulvar cancer is a rare gynaecological cancer with increasing incidence rate in the past decades, especially among the Indigenous population and human papillomavirus (HPV) prevalent areas. However, due to low incidence rate, only limited numbers of tumour samples are available, here we use complementary mass-spectrometric approaches to identify tumour specific diagnostic and prognostic biomarkers. Mass spectrometry based proteomics analysis for protein discovery has been successfully applied on gynaecological cancers. MALDI-Imaging MS and Label-free quantification MS are able to quantify numerous proteins from different morphological features, which are ideal tools for studying current vulvar cancer proteomics patterns. To investigate vulvar cancer tissue unique proteomics patterns, MALDI-Imaging and LFQ MS have been performed using FFPE tissue blocks from four vulvar cancer patients. Statistics software was used for spectra training and peak matching on different platforms. We have identified 1400 proteins from all samples and half of them are unique to specific tissue types. Based on these analyses, we can discriminate between healthy and tumour and have identified a few proteins which are up regulated during cancer development. Furthermore, RNA-sequencing will be introduced to complement current protein databases with transcriptomic data.  In summary, our approach provides valuable insight into vulvar cancer development.