Structural studies show that fish and mammalian metallothioneins are endowed of distinctive features. In particular, the ninth cysteine residue present in the alpha domain of fish metallothionein is shifted of two positions with respect to the mammalian metallothionein, introducing a conformational modification in the protein structure. In addition, the fish metallothionein is less hydrophobic and more flexible than its mammalian counterpart. Our previous studies showed that the hydropathy of piscine and mammalian metallothioneins is significantly correlated with organismal temperature. In the present paper we have performed phylogenetic comparative analysis on metallothioneins of 24 species of fish and mammals. The results of such analysis failed to indicate that metallothionein hydropathy is an adaptive response to the thermal regime of the species. We concluded that metallothionein hydropathy is a trait that did not evolve in association with environmental changes.