Domoic acid (DA) is a potent neurotoxin produced by diatoms of the genus Pseudo-nitzschia and is responsible for Amnesic Shellfish Poisoning (ASP) in humans. Some fishery resources of high commercial value, such as the king scallop Pecten maximus, are frequently exposed to toxic Pseudo-nitzschia blooms and are capable of accumulating high amounts of DA, retaining it for months or even a few years. This poses a serious threat to public health and a continuous economical risk due to fishing closures of this resource in the affected areas. Recently, it was hypothesized that trapping of DA within autophagosomic-vesicles could be one reason explaining the long retention of the remaining toxin in P. maximus digestive gland. To test this idea, we follow the kinetics of the subcellular localization of DA in the digestive glands of P. maximus during (a) the contamination process — with sequential samplings of scallops reared in the field during 234 days and naturally exposed to blooms of DA-producing Pseudo-nitzschia australis, and (b) the decontamination process — where highly contaminated scallops were collected after a natural bloom of toxic P. australis and subjected to DA-depuration in the laboratory for 60 days. In the digestive gland, DA-depuration rate (0.001 day−1) was much slower than contamination kinetics. The subcellular analyses revealed a direct implication of early autophagy in DA sequestration throughout contamination (r = 0.8, P < 0.05), while the presence of DA-labeled residual bodies (late autophagy) appeared to be strongly and significantly related to slow DA-depuration (r = -0.5) resembling an analogous DA-tattooing in the digestive glands of P. maximus. This work provides new evidence about the potential physiological mechanisms involved in the long retention of DA in P. maximus and represents the baseline to explore procedures to accelerate decontamination in this species.