The structure of tyrosinase (Tyr) is reviewed from a double point of view. On the one hand, by comparison of all Tyr found throughout nature, from prokaryotic organisms to mammals and on the other, by comparison with the tyrosinase related proteins (Tyrps) that appeared late in evolution, and are only found in higher animals. Their structures are reviewed as a whole rather than focused on the histidine (His)-bound metal active site, which is the part of the molecule common to all these proteins. The availability of crystallographic data of hemocyanins and recently of sweet potato catechol oxidase has improved the model of the three-dimensional structure of the Tyr family. Accordingly, Tyr has a higher structural disorder than hemocyanins, particularly at the CuA site. The active site seems to be characterized by the formation of a hydrophobic pocket with a number of conserved aromatic residues sited close to the well-known His. Other regions specific of the mammalian enzymes, such as the cytosolic C-terminal tail, the cysteine clusters, and the N-glycosylation sequons, are also discussed. The complete understanding of the Tyr copper-binding domain and the characterization of the residues determinant of the relative substrate affinities of the Tyrps will improve the design of targeted mutagenesis experiments to understand the different catalytic capabilities of Tyr and Tyrps. This may assist future aims, from the design of more efficient bacterial Tyr for biotechnological applications to the design of inhibitors of undesirable fruit browning in vegetables or of color skin modulators in animals.