The superficial chemical heterogeneity of sulphide minerals can be natural or induced. Comminution is one possible way for changing, sometimes drastically, the surface state of sulphides, which, consequently, modifies the reactivity of the divided solid. Using different investigation techniques at the molecular scale, the chemical nature of the surface of galena, pyrite, chalcopyrite and sphalerite after various comminution conditions can be precisely described. Galena and pyrite are partially covered with piles of oxidized sulphates and carbonates species. Elemental sulfur was also revealed in variable amounts. After wet grinding, the chalcopyrite surface is altered by the formation of a continuous 200-nm-thick layer iron oxy-hydroxides. Xanthate molecules can be used as molecular probes for describing the surface of ZnS after wet grinding.