Background: Scylla paramamosain frequently elicits IgE-mediated type-I hypersensitivity reactions. Molecular candidates for crab allergen-specific immunotherapy (AIT) have not been studied previously. This study aimed to investigate the effects of conformational and linear epitopes on immunoreactivity, and to produce hypo-immunoreactive derivatives for crab myofibril allergens. Methods: We produced reduced and alkylated allergens (alkylation performed using iodoacetamide [IAA]) with destroyed conformational epitopes. We also produced mutant (mt) allergens with deleted or heat/digestion-treated linear epitopes. These allergens are collectively referred to here as derivatives. Structural changes in the derivatives were determined using circular dichroism and fluorescent probes, and the immunoreactivity of derivatives was analyzed by performing enzyme-linked immunosorbent assays (ELISAs) and basophil-activation tests (BATs). Results: Compared with wild-type allergens (wtALLERGENs), IAA-treated allergens had dramatically altered protein structures, whereas mutant allergens (mtALLERGENs) showed slight structural effects. ELISAs revealed the heterogeneous epitope-recognition patterns with derivatives among 29 crab-sensitive patients, of whom 13% and 62% recognized conformational and linear epitopes, respectively, whereas 25% recognized both epitope types to the same extent. mtALLERGENs had lower immunoreactivity than IAA-treated wtALLERGENs, showing no intergroup difference versus IAA-treated mtALLERGENs. Furthermore, mtALLERGENs could not bind to IgE or induce basophil activation in some patients. Conclusions: Heat/digestion treatment of linear epitopes had a greater influence on immunoreactivity than their structural destruction. Conformational and linear epitopes were recognized in patient-specific crab myofibril allergens. Our results imply that hypo-immunoreactive derivatives of crab myofibril allergens that specifically lacked linear epitopes may serve as viable candidates for AIT in patients with crab allergies.