Grappa is the traditional Italian spirit derived from marc. The molecular characterization of volatile compounds in the liquid Grappa, responsible of its bouquet, has been achieved by headspace solid-phase microextraction (HS-SPME) followed by gas chromatography–mass spectrometry (GC-MS). Of these, 12 compounds represent more than 1% of Grappa volatile fraction.In addition, a molecular fingerprint of Grappa samples was performed by MALDI-TOF and MALDI-TOF/TOF MS, allowing the identification of molecular structures of major compounds within the non-volatile fraction of Grappa. The −82Da shifts on precursor ion masses due to the loss of 5-methylfuran ion also allowed the identification of some heterocyclic compounds, such as furan derivatives, formed during the Grappa aging within barrels. Overall, by integrating different mass spec techniques, we obtained a comprehensive molecular fingerprint of selected Grappa samples.