The envisaged promotion of local products contributes to environmental protection and is a valid tool for the promotion of socioeconomic development, enhancement of territories, and biodiversity preservation and sustainability. Provolone del Monaco is a semi hard pasta filata cheese granted PDO (Protected Designation of Origin) designation by the European Union. Provolone del Monaco is obtained from raw cow’s milk, produced in the specific areas of the Lattari Mountains and Sorrento Peninsula (Naples, Italy), and ripened for at least six months. To the best of our knowledge, no studies concerning the complete chemical characterization of Provolone del Monaco cheese are available. In the present study; the chemical characterization (moisture; pH; titratable acidity; nitrogen; and fat content), fatty acid composition determined by using gas-chromatography-flame-ionization-detector (GC-FID); volatile organic compounds by solid-phase microextraction followed by gas chromatography-mass spectrometry (SPME-GC/MS), and maturation indices were evaluated during ripening. Two different average typical cheese sizes (3 kg and 5 kg) and two different internal portions were studied. After 6 months of ripening, the most important changes recorded were the loss of water, the increase in acidity, the nitrogen (as ammonia) release, and the production of volatile organic compounds. The cheese size did not affect the chemical composition of Provolone del Monaco.