Background Mucosal melanoma (MM) is a rare but diverse cancer entity. Prognostic factors are not well established for Caucasians with MM. Patients and methods We analysed the disease course of 444 patients from 15 German skin cancer centres. Disease progression was determined with the cumulative incidence function. Survival times were estimated with the Kaplan–Meier method. Prognostic parameters were identified with multivariate Cox regression analysis. Results Common anatomic sites of primary tumours were head and neck (MMHN, 37.2%), female genital tract (MMFG, 30.4%) and anorectal region (MMAN, 21.8%). MMAN patients showed the highest vertical tumour thickness (p = 0.001), had a more advanced nodal status (p = 0.014) and a higher percentage of metastatic disease (p = 0.001) at diagnosis. Mutations of NRAS (13.8%), KIT (8.6%) and BRAF (6.4%) were evenly distributed across all tumour site groups. Local relapses were observed in 32.4% and most commonly occurred in the MMHN group (p = 0.016). Male gender (p = 0.047), advanced tumour stage (p = 0.001), nodal disease (p = 0.001) and incomplete resection status (p = 0.001) were independent risk factors for disease progression. Overall survival (OS) was highest in the MMFG group (p = 0.030) and in patients without ulceration (p = 0.004). Multivariate risk factors for OS were M stage at diagnosis (p = 0.002) and incomplete resection of the primary tumour (p = 0.001). Conclusion In this large series of MM patients in a European population, anorectal MM was associated with the poorest prognosis.