Domoic acid (DA), the toxin responsible for the illness known as amnesic shellfish poisoning (ASP), is an algal toxin produced naturally by some species of the diatom genus Pseudo-nitzschia. The toxin has been detected in a diverse array of marine organisms from copepods to whales. Cephalopods, which are important members of the food chain and active predators of known toxin vectors such as bivalves, crabs and some fishes, have just recently been implicated in DA transfer or accumulation. Here we present data showing detectable values of DA determined by HPLC-UV (high-performance liquid chromatography and ultraviolet detection) and confirmed by HPLC-MS (mass spectrometric detection) in two octopus species collected along the Portuguese continental coast: Eledone cirrhosa and E. moschata. Domoic acid was frequently detected in the digestive gland of E. moschata and occasionally reached concentrations exceeding 100 µg g−1. In contrast, E. cirrhosa contained lower concentrations of DA on the few occasions that it was detected. This suggests that E. moschata is a potential vector for DA transfer to higher trophic levels in the coastal marine food web, not excluding humans. These data, combined with known aspects of the life history of the species, are a necessary step towards achieving an understanding of the accumulation of phycotoxins in cephalopods.