The increasing production and consumption of molluscs are associated with a rise in the prevalence of mollusc allergy worldwide, currently affecting 0.2% to 1.3% of the general population. However, the elucidation of mollusc allergens, crucial for better diagnostics, still lags behind other seafood groups such as fish and crustacean. Genomic data have previously been utilized for the improved identification of non-food allergens by performing similarity searches using the BLAST program. Based on the published genome of the Pacific oyster (Crassostrea gigas) we aimed to identify the repertoire of potential allergen using bioinformatics analysis and sought to validate allergenicity using a combination of immuno-chemical methods and proteomic analysis. A repertoire of 25,982 genome-derived proteomes of the Pacific oyster were aligned with 2117 allergen sequences resulting in over 800 protein homologues. Of those, 95 proteins were potentially cross-reactive allergens due to high identity with known allergens (>50% identity). Analysis of the transcriptomic data showed the proteins were differentially expressed across tissue of the oyster.