Cutaneous melanoma has the lowest survival rate of all forms of skin cancer. There has been little research investigating the link between arsenic and cutaneous melanoma, although arsenic has been associated with increased risk of nonmelanoma skin cancer. The authors performed a case-control study examining the association between cutaneous melanoma and environmental arsenic exposure among Iowans aged 40 years or older. Participants included 368 cutaneous melanoma cases and 373 colorectal cancer controls diagnosed in 1999 or 2000, frequency matched on gender and age. Participants completed a mailed survey and submitted toenail clippings for analysis of arsenic content by graphite furnace atomic absorption spectrophotometry. The authors found an increased risk of melanoma for participants with elevated toenail arsenic concentrations (odds ratio = 2.1, 95 percent confidence interval: 1.4, 3.3; p-trend = 0.001) and effect modification by prior skin cancer diagnosis (p-interaction = 0.03). The arsenic-melanoma findings in this study are not known to have been previously reported in observational epidemiologic studies involving incident cutaneous melanoma. Therefore, the findings warrant confirmation.