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Background: The COVID-19 pandemic has produced devastating effects on the health care system, also affecting cancer patient care. When the pandemic reached Spain by the end of February 2020, the scarce data about COVID-19 infection in cancer patients pointed out a higher risk of complications due to cancer diagnosis and also to cancer therapies. These conjectures led to concerns about hospital follow-up and cancer therapies of cancer patients. More recent studies have included a higher number of patients, but heterogeneous according to cancer type and tumor stage, with few melanoma patients recorded. Given that different tumor types are associated with specific comorbidities that have a known impact on COVID-19 evolution, analysis of COVID-19 by cancer types is mandatory. Similarly, analysis by tumor stage is relevant, as advanced cases could have different responses to viral infection due to tumor-related immunosuppression and general condition deterioration. Methods: In Spain we have completed a national registry of melanoma patients infected by SARS-Cov-2 since April 1st, 2020 to June 8th, 2020. Patients with a previous diagnosis of melanoma, presenting with Sars-Cov-2 infection to our network of hospitals, were eligible for enrollment. A prospective observational study with a case registry followed by a retrospective analysis of patient data has been performed. Results: 64 patients have been included. Median age is 68 years (range 6 to 95 years), 22 (34%) patients are females, and 35 (55%) patients have stage IV melanoma. Twenty-one (33%) patients were on active anticancer treatment with anti PD-1 antibodies, 19 (30%) patients with BRAF plus MEK inhibitors, and 24 (37%) patients were not on active treatment. Asymptomatic/paucisymptomatic evolution was recorded in 19 (30%) patients and mild severity in 13 (20%) patients, not requiring hospital admission by COVID-19. Serious and life-threatening complications were recorded in 18 (28%) and 14 (22%) patients, respectively, including 28 (44%) patients who required oxygen therapy and 3 (5%) patients who had ICU admission. COVID-19 episode is resolved in 55 cases, including 34 (53%) patients cured, eight (12%) patients who have died due to melanoma progression, and 13 (20%) patients due to COVID-19. The median age of patients who died from COVID-19 was 74 years (range 49 to 91), while for those cured it was 64 years (range 6 to 95); 85% of patients who died were males, while this rate decreased to 62% for those cured. The mortality rate from COVID-19 was 20% for both stage IV and localized melanoma, while according to melanoma treatment it was 21%, 16%, and 21% for immunotherapy, BRAF plus MEK inhibitors, and for those who were not undergoing active cancer treatment, respectively. Conclusion: Our results show that the risk of death in melanoma patients is higher in males and older patients, and it is similar according to tumor stage and melanoma therapy. The impact of cancer diagnosis and treatments on COVID-19 evolution is lower than previously expected. Citation Format: Maria Gonzalez-Cao, Cristina Carrera, Juan Francisco Rodriguez Moreno, Pedro Rodriguez-Jiménez, Mónica Antoñanzas Basa, Marta Feito Rodríguez, Teresa Puertolas, Eva Muñoz, José Luis Manzano, Ivan Marquez-Rodas, Juan Martín-Liberal, Ainara Soria, Pilar Lopez Criado, Almudena García Castaño, Aram Boada, Pablo Ayala de Miguel, Susana Puig, Guillermo Crespo, Pablo Luna Fra, Cristina Aguayo Zamora, Jesús Gardeazabal, Cayetana Maldonado Seral, Ana Drozdowskyj, Mariano Provencio, Alfonso Berrocal. COVID-19 in melanoma patients: Spanish register [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-059.