Mouse prostaglandin EP3 receptor consists of three isoforms, EP3α, β and γ, with different carboxy‐terminal tails. To assess the role of their carboxy‐terminal tails in membrane targeting, we examined subcellular localization of myc‐tagged EP3 isoforms expressed in MDCK cells. Two isoforms, EP3α and EP3β, were localized in the intracellular compartment but not in the plasma membrane, while the EP3γ isoform was found in the lateral plasma membrane and in part in the intracellular compartment. Mutant EP3 receptor lacking the carboxy‐terminal tail was localized in the intracellular compartment but not in the plasma membrane. Thus, EP3 isoforms differ in subcellular targeting, and the carboxy‐terminal tails play an important role in determination of the membrane targeting of EP3 receptor.