Ciguatera is a foodborne disease caused by the consumption of seafood contaminated with ciguatoxins (CTXs). Ciguatera-like poisoning events involving giant clams (Tridacna maxima) are reported occasionally from Pacific islands communities. The present study aimed at providing insights into CTXs tissue distribution and detoxification rate in giant clams exposed to toxic cells of Gambierdiscus polynesiensis, in the framework of seafood safety assessment. In a first experiment, three groups of tissue (viscera, flesh and mantle) were dissected from exposed individuals, and analyzed for their toxicity using the neuroblastoma cell-based assay (CBA-N2a) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses. The viscera, flesh, and mantle were shown to retain 65%, 25%, and 10% of the total toxin burden, respectively. All tissues reached levels above the safety limit recommended for human consumption, suggesting that evisceration alone, a practice widely used among local populations, is not enough to ensure seafood safety. In a second experiment, the toxin content in contaminated giant clams was followed at different time points (0, 2, 4, and 6 days post-exposure). Observations suggest that no toxin elimination is visible in T. maxima throughout 6 days of detoxification.