Conserved sequence identity between shellfish allergens has been described but clinical significance is poorly understood. We present a patient with negative commercial skin prick testing (SPT) and serum specific IgE (sIgE) testing to crab but anaphylaxis with oral food challenge (OFC) to snow crab despite sustained oral tolerance to blue crab and other shellfish. SPT was preformed to house dust mite (HDM), fresh crabs and commercial crab extract, as well as sIgE to crab. Western blot analysis was conducted using patient serum on crude protein extracts isolated from different crab species, SPT reagents and tropomyosin. SPT was positive to HDM but negative to shellfish, including crab (Atlantic blue crab, Callinectes sapidus). Crab sIgE (snow crab, Chionoecetes opilio) <0.10 kU/L and total IgE 19 IU/mL. SPT to fresh, steamed, unseasoned crabmeat was 3mm to Dungeness and King crabs and 1mm to snow crab. Patient developed urticaria, nausea and severe abdominal pain after the second OFC dose (less than 3g snow crab protein). In western blot analysis, the IgE profile was unremarkable when patient serum was compared to serum obtained from a control. In the same analysis, while the patient serum was positive to HDM, patient was negative for IgE to tropomyosin. Our studies demonstrate limitations of current diagnostic approaches in capturing allergy to specific crab species. Additional studies with inclusion of more patients, extract lots, and expanded individual shellfish should provide more detailed insights into shellfish allergy and understanding of diagnostic extract and variability.