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Simple Summary: Immunotherapy revolutionized the treatment of cutaneous melanoma and greatly improved treatment outcomes in this group of patients. Mucosal melanoma is a rare disease, biologically distinct from the cutaneous subtype. There is little real-world data on immunotherapy efficacy in mucosal melanoma. Therefore, we aimed to analyze and describe experiences in mucosal melanoma treatment in five high volume oncology centers in Europe. Furthermore, we evaluated if concomitant radiotherapy may improve the outcomes of these patients. We conclude that immunotherapy with anti-PD1 antibodies is a safe and effective treatment of mucosal melanoma. Concomitant radiotherapy may be beneficial in a selected subgroup of patients with advanced mucosal melanoma. Mucosal melanoma is a rare disease epidemiologically and molecularly distinct from cutaneous melanoma developing from melanocytes located in mucosal membranes. Little is known about its therapy. In this paper, we aimed to evaluate the results of immunotherapy and radiotherapy in a group of patients with advanced mucosal melanoma, based on the experience of five high-volume centers in Poland and Italy. There were 82 patients (53 female, 29 male) included in this retrospective study. The median age in this group was 67.5 (IQR: 57.25–75.75). All patients received anti-PD1 or anti-CTLA4 antibodies in the first or second line of treatment. Twenty-three patients received radiotherapy during anti-PD1 treatment. In the first-line treatment, the median progression-free survival (PFS) reached six months in the anti-PD1 group, which was statistically better than 3.1 months in the other modalities group (p = 0.004). The median overall survival (OS) was 16.3 months (CI: 12.1–22.3) in the whole cohort. Patients who received radiotherapy (RT) during the anti-PD1 treatment had a median PFS of 8.9 months (CI: 7.4–NA), whereas patients treated with single-modality anti-PD1 therapy had a median PFS of 4.2 months (CI: 3.0–7.8); this difference was statistically significant (p = 0.047). Anti-PD1 antibodies are an effective treatment option in advanced mucosal melanoma (MM). The addition of RT may have been beneficial in the selected subgroup of mucosal melanoma patients. [ABSTRACT FROM AUTHOR]