Metallothioneins (MTs) are ubiquitous proteins with the capacity to bind heavy metal ions (mainly Cd, Zn or Cu), and they have been found in animals, plants, eukaryotic and prokaryotic micro-organisms. We have carried out a comparative analysis of ciliate MTs (Tetrahymena species) to well-known MTs from other organisms, discussing their exclusive features, such as the presence of aromatic amino acid residues and almost exclusive cysteine clusters (CCC) present in cadmium-binding metallothioneins (CdMTs), higher heavy metal-MT stoichiometry values, and a strictly conserved modular-submodular structure. Based on this last feature and an extensive gene duplication, we propose a possible model for the evolutionary history of T. thermophila MTs. We also suggest possible functions for these MTs from consideration of their differential gene expressions and discuss the potential use of these proteins and/or their gene promoters for designing molecular or whole-cell biosensors for a fast detection of heavy metals in diverse polluted ecosystems.