Tumors of the female reproductive tract are an important target for the development of diagnostic, prognostic and therapeutic strategies. Recent research has turned to proteomics based on mass spectrometry techniques, to achieve more effective diagnostic results. Mass spectrometry (MS) enables identification and quantification of multiple molecules simultaneously in a single experiment according to mass to charge ratio (m/z). Several proteomic strategies may be applied to establish the function of a particular protein/peptide or to identify a novel disease and specific biomarkers related to it. Therefore, MS could facilitate treatment in patients with tumors by helping researchers discover new biomarkers and narrowly targeted drugs. This review presents a comprehensive discussion of mass spectrometry as a tool for biomarkers searching that may lead to the discovery of easily available diagnostic tests in gynecological oncology with emphasis on clinical proteomics over the past decade. The article provides an insight into different MS based proteomic approaches.