Background: The value of laboratory tests in chronic urticaria is still controversial. Objective: Our aim was to assess this value in clinical studies, and to identify factors explaining the variation in the number of identified causes. Methods: A total of 4 electronic databases were searched, and a manual literature search was performed. Only unselected patient series with more than 50 adult patients were included. From each included study predefined items were recorded to assess their quality (consecutive patients, use of standardized diagnostic criteria) and validity (follow-up, assessment of treatment effects, level of evidence). Results: A total of 29 studies were included, involving 6462 patients. The verification of the validity of the results and the level of evidence of the included studies were limited. Conclusion: No relationship between the number of identified diagnoses and the number of performed laboratory tests, the different settings, the study design, or the publication period was found. On the basis of this systematic review and the relevant literature, a clinical guideline in the form of a flowchart is presented. (J Am Acad Dermatol 2003;48:409-16.)