BACKGROUND: Originally developed to protect against sunburn, sunscreen has been assumed to prevent skin cancer. However, conflicting reports include claims that sunscreen increases risk for melanoma. OBJECTIVE: To examine the strength and consistency of associations between melanoma and sunscreen use in the published literature. DATA SOURCES: A comprehensive MEDLINE search of articles published from 1966 to 2003 that reported information on sunscreen use and melanoma in humans. STUDY SELECTION: Analytic studies reporting data on sunscreen use before diagnosis of melanoma. DATA EXTRACTION: Two independent reviewers extracted data. Inconsistencies were rereviewed until agreement was achieved. When necessary, a third party resolved discrepancies. DATA SYNTHESIS: Odds ratios were pooled across studies by using standard meta-analytic techniques. Pooled odds ratios for ever use among 18 heterogeneous studies did not support an association between melanoma and sunscreen use. Variation among odds ratios was explained by studies that did not adjust for confounding effects of sun sensitivity. The lack of a dose-response effect with frequency of use (never, sometimes, or always) or years of use provided further evidence of a null association. CONCLUSIONS: No association was seen between melanoma and sunscreen use. Failure to control for confounding factors may explain previous reports of positive associations linking melanoma to sunscreen use. In addition, it may take decades to detect a protective association between melanoma and use of the newer formulations of sunscreens.