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Background/Aim: Breast cancer (BC) incidence and mortality rates have been increasing due to the lack of appropriate diagnostic tools for early detection. Proteomicsbased studies may provide novel targets for early diagnosis and efficient treatment. The aim of this study was to investigate the global changes occurring in protein profiles in breast cancer tissues to discover potential diagnostic or prognostic biomarkers. Materials and Methods: BC tissues and their corresponding healthy counterparts were collected, subtyped, and subjected to comparative proteomics analyses using two-dimensional gel electrophoresis (2-DE) and twodimensional electrophoresis fluorescence difference gel (DIGE) coupled to matrix-assisted laser desorption/ ionisation-time of flight mass spectrometry (MALDITOF/TOF) to explore BC metabolism at the proteome level. Western blot analysis was used to verify changes occurring at the protein levels. Results: 210Bioinformatics analyses performed with differentially regulated proteins highlighted the changes occurring in triacylglyceride (TAG) metabolism, and directed our attention to TAG metabolism-associated proteins, namely glycerol-3-phosphate dehydrogenase 1 (GPD1) and monoacylglycerol lipase (MAGL). These proteins were downregulated in tumor groups in comparison to controls. Conclusion: GPD1 and MAGL might be promising tissue-based protein biomarkers with a predictive potential for BC.