AbstractTerrestrial gastropods express metal‐selective metallothioneins (MTs) by which they handle metal ions such as Zn2+, Cd2+, and Cu+/Cu2+through separate metabolic pathways. At the same time, they depend on the availability of sufficient amounts of Cu as an essential constituent of their respiratory protein, hemocyanin (Hc). It was, therefore, suggested that in snails Cu‐dependent MT and Hc pathways might be metabolically connected. In fact, the Cu‐specific snail MT (CuMT) is exclusively expressed in rhogocytes, a particular molluscan cell type present in the hemocoel and connective tissues. Snail rhogocytes are also the sites of Hc synthesis. In the present study, possible interactions between the metal‐regulatory and detoxifying activity of MTs and the Cu demand of Hc isoforms was explored in the edible snailCornu aspersum, one of the most common European helicid land snails. This species possesses CdMT and CuMT isoforms involved in metal‐selective physiological tasks. In addition,C. aspersumexpresses three different Hc isoforms (CaH ɑD, CaH ɑN, CaH β). We have examined the effect of Cd2+and Cu2+exposure on metal accumulation in the midgut gland and mantle ofC. aspersum, testing the impact of these metals on transcriptional upregulation ofCdMT,CuMT, and the threeHcgenes in the two organs. We found that theCuMTandCaH ɑDgenes exhibit an organ‐specific transcriptional upregulation in the midgut gland of Cu‐exposed snails. These results are discussed in view of possible interrelationships between the metal‐selective activity of snail MT isoforms and the synthesis and metabolism of Hc isoforms.