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Background: Mastocytosis encompasses a spectrum of disorders in which different organs and tissues are affected by the clonal expansion of mast cells. The skin is one of the most frequently affected organs. The clinical manifestations of mastocytosis are linked to the release of proinflammatory mediators, and the impact of this disorder on patient quality of life has been described in various studies. The Mastocytosis Quality of Life Questionnaire (MC-QoL), which was recently developed in Germany and now also exists in English, is an important tool for evaluating the psychosocial impact of this disease. Objective: To create a Spanish version of the MC-QoL that was culturally equivalent to the original German questionnaire. Material and methods: The adaptation process, which involved forward translation, cognitive interviews, and back translation, was conducted in accordance with the principles of good practice for the translation and cultural adaptation of patient-reported measures of the International Society for Pharmacoeconomics and Outcomes Research. The MC-QoL contains 27 items in 4 domains: symptoms, emotions, social life/functioning, and skin. Results: The first version of the Spanish questionnaire, obtained by direct translation from German, was tested in cognitive interviews, after which 3 items were modified to make them easier to understand. The German back translation of the Spanish questionnaire was analyzed by the authors of the original MC-QoL, who modified 1 item they considered to have lost specificity in the adaptation process. The definitive Spanish MC-QoL was then produced following minor modifications agreed on with the German authors.