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There are both semantic and technical differences between land use (LU) and land cover (LC) measurements. In cartographic approaches, these differences are often neglected, giving rise to a hybrid classification. The aim of this paper is to provide a better understanding and characterization of the two classification schemes using a comparison that allows maximization of the informative power of both. The analysis was carried out in the Molise region (Central Italy) using sample information from the Italian Land Use Inventory (IUTI). The sampling points were classified with a visual interpretation of aerial photographs for both LU and LC in order to estimate surfaces and assess the changes that occurred between 2000 and 2012. The results underscore the polarization of land use and land cover changes resulting from the following: (a) recolonization of natural surfaces, (b) strong dynamisms between the LC classes in the natural and semi-natural domain and (c) urban sprawl on the lower hills and plains. Most of the observed transitions are attributable to decreases in croplands, natural grasslands and pastures, owing to agricultural abandonment. The results demonstrate that a comparison between LU and LC estimates and their changes provides an understanding of the causes of misalignment between the two criteria. Such information may be useful for planning policies in both natural and semi-natural contexts as well as in urban areas.