Mastocytosis is a myeloproliferative neoplasm characterized by infiltration of clonally derived mast cells in different tissues. According to mast cells localization, it is possible to discriminate cutaneous mastocytosis (CM) from systemic mastocytosis (SM), the latter involving at least an extracutaneous organ, like bone marrow, liver, spleen and gastrointestinal tract. Some of the SM patient can develop also cutaneous lesions (SM+C). Disease classification is often tricky. Oral cavity is commonly involved in the symptomatology. With the aim to highlight possible qualitative/quantitative modifications of the salivary proteome associated to the different forms of the disease, we investigated the protein profiles of CM, SM, and SM+C patients, and healthy controls, by integrated top-down platforms. a top-down proteomic platform, based on high performance liquid chromatography separation coupled to electrospray-ion trap mass spectrometry (HPLC-ESI-IT-MS) analysis of the acidic soluble proteome of human saliva, which was standardized in our previous studies for detecting and quantifying of hundreds salivary peptides/proteins. By this approach, it is possible to obtain a profiling of the naturally occurring salivary proteome, including isoforms and post-translational modifications (PTMs), to compare an unlimited number of samples and to quantify proteins aby a label-free method.