Background: Clinical trials enroll patients with specific diseases based on certain pre-defined eligibility criteria. Disease registries are crucial to evaluate the efficacy and safety of new expensive oncology medicines in broad non-trial patient populations. Methods: We provide detailed information on the structure, including variables, and the scientific results from a nation-wide Danish database covering advanced melanoma, illustrating the importance of continuous real-world data registration. Disease status and treatment-related information on all patients with American Joint Committee on Cancer (AJCC) 8th edition stage III or IV melanoma candidates to medical treatment in Denmark are prospectively registered in the Danish Metastatic Melanoma Database (DAMMED). Results: By January 1st, 2021, DAMMED includes 4156 patients and 7420 treatment regimens. Response rates and survival data from published randomized clinical trial data are compared with real-world efficacy data from DAMMED and presented. Overall, nine independent manuscripts highlighting similarities and discrepancies between real-world and clinical trial results are already reported to date. Conclusion: Nation-wide disease registries take into consideration the complexity of daily clinical practice. We show a concrete example of how disease registries can complement clinical trials' information, improving clinical practice, and support health-related technology assessment.