Abstract: Divining the functional role of proteins in life processes, starting from their structural features, is the challenging purpose of structural biology. In this context, SCOP and CATH databases are the starting point for scientist aiming at discovering the relationships between function and molecular structure. The classification criteria adopted are based on the topological architecture of the molecule, thus the proteins are clustered by finding local folding motifs which are repeatedly encountered in the protein data bank. It is an assumption largely accepted that the overall structure deserves the appropriate distribution of chemical properties on the surface that the protein presents to its molecular target. Thanks to its “appearance” the protein could have the correct approach with the target or not. However, two proteins with similar structures may be divergent in their sequence, thus playing different functions. The structural classification as a tool for the individuation of a common physiological role is misleading in this case and a surface classification is more and more reputed necessary. Up to now, a successful strategy has not yet developed to reach such a general goal: the most exploited approach consists in adopting a surface patch already recognized to play a key role for a certain function and use it as a probe to explore the surfaces of all the proteins with known structure. This method, based on local features, will fail in all cases characterized by highly adaptable surfaces and when portions of surface far from the active site have a dominant allosteric effect on the functional region of the protein. In this paper we propose an original approach to classification of proteins based on their surface characteristics, which has the advantage of being not based on local surface features neither on already known functional meanings.