Melon (Cucumis melo L.), belonging to the Cucurbitaceae family, is a significant source of phytochemicals which provide human health benefits. High-performance liquid chromatography coupled to electrospray ionization mass spectrometry quadropole-time of flight (HPLC-ESI-QTOF-MS) was used for the comprehensive characterization of 14 extracts from 3 Spanish varieties of melon (Galia, Cantaloupe, and Piet de Sapo). A total of 56 different compounds were tentatively identified, including: amino acids and derivatives, nucleosides, organic acids, phenolic acids and derivatives, esters, flavonoids, lignans, and other polar compounds. Of these, 25 were tentatively characterized for the first time in C. melo varieties. Principal-component analysis (PCA) was applied to gain an overview of the distribution of the melon varieties and to clearly separate the different varieties. The result of the PCA for the negative mode was evaluated. The variables most decisive to discriminate among varieties included 12 of the metabolites tentatively identified. (C) 2013 Elsevier Ltd. All rights reserved.