BACKGROUND: From July 1, 2003 to June 30, 2004, a population‐based skin cancer screening project was conducted in Schleswig‐Holstein, Germany. In total, 360,288 individuals aged ≥20 years were screened by means of a whole‐body examination. In this report, the authors compare trends in melanoma mortality in Schleswig‐Holstein with those in all adjacent regions, none of which had population‐based skin cancer screening. METHODS: Trends in melanoma mortality rates for Schleswig‐Holstein and the adjacent regions (Denmark and the German federal states of Mecklenburg‐Vorpommern, Hamburg, and Lower Saxony) and in Germany excluding Schleswig‐Holstein were compared. Log‐linear regression was used to assess mortality trends. RESULTS: In Schleswig‐Holstein during the pre skin cancer screening period (1998‐1999), the age‐standardized melanoma mortality rate (World standard population) was 1.9 per 100,000 for men and 1.4 per 100,000 for women. Melanoma mortality declined by 47% to 1.0 per 100,000 men and by 49% to 0.7 per 100,000 women by 2008/2009. The annual percentage change in the most recent 10‐year period (2000‐2009) was −7.5% (95% confidence interval, −14.0, −0.5) for men and −7.1% (95% confidence interval, −10.5, −2.9) for women. In each of the 4 adjacent regions and in the rest of Germany, mortality rates were stable, and the decline in Schleswig‐Holstein was significantly different from the changes observed in all of the other areas studied. CONCLUSIONS: The current data represent strong evidence, but not absolute proof, that the skin cancer screening program produced a reduction in melanoma mortality in Schleswig‐Holstein. Cancer 2012. © 2012 American Cancer Society.