Allergens from crustaceans and mollusks exhibit extensive cross-reactivity in vitro. However, the degree and pattern of cross-reactivity between different shellfish species in vivo is still unclear. The objective of this study was to determine the clinical characteristics of shellfish allergic patients in Hong Kong and the pattern of skin test reactivities to the different species. This cohort study involves patients attending the allergy clinic of a large teaching hospital for suspected shellfish allergy. Each subject underwent skin-prick tests to eight species of shellfish and house-dust mites. Eighty-four consecutive patients were tested. Twenty-eight patients reported a history of severe anaphylaxis. Fourteen patients had no positive shellfish skin test and were excluded. There were 183 positive shellfish skin tests, with an average of 2.61 positive tests per subject. Ninety percent of subjects also had positive skin tests to house-dust mites. Overall, 65. 7% of subjects had more than one positive skin test to shellfish. There were strong statistical associations between species belonging to the same order but also between some mollusks and crustaceans. We found a high degree of skin test cross-reactivity between different species of shellfish and between shellfish and house-dust mites. Therefore, patients with a history of shellfish allergy should be cautious with all types of shellfish.