Background: Positive patch tests to copper sulfate are regularly observed, although copper is reported as a rare allergen with a low sensitizing potential. Usually they are claimed to be irritant and unspecific. Objective: The aim of this study was to assess the relevance and the diagnostic value of positive reactions to copper. Methods: A total of 2660 routine patch tests were analyzed for positive reactions to copper and other metal allergens: copper, 3.53%; nickel, 21.02%; palladium, 5.90%; cobalt, 3.31%. Results: Reactions to copper and nickel were highly significantly associated with each other. Twenty-six patients with a positive routine test to copper were retested. The reproducibility was modest (38%), but again significantly associated with nickel sensitization. Conclusion: These clinical data support a copper-nickel cross-reactivity concept on T-cell level based on recently published molecular data. We conclude that positive patch tests to copper are mostly specific; however, they are usually of low clinical relevance. (J Am Acad Dermatol 2001;45:863-70.)