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Introduction Mucosal melanomas (MM) of the female genital tract are rare a. We aimed to study the prognostic factors of vulvar and vaginal locations of MM. Material and method A multicenter, retrospective cohort study conducted between 01/01/2000 and 01/06/2019. Result Of the 33 patients included 25 (75.8 %) had vulvar (VuM) and eight (24.2 %) vaginal melanomas (VaM). VaMs were deeper: median Breslow index: 17.5 mm [3.5−22] versus 4.3 mm [0.35−18] (p = 0.013). Average follow-up was 24.0 ± 59.8 months. Twenty-six patients (78.8 %) experienced recurrence. Disease-free survival was 52.9 % at 1 year (64.7 % for VuM and 14.3 % for VaM) and 8.4 % at 3 years (11 % for VuM and 0% for VaM) (p = 0.002). Median time to the first recurrence was 9.01 months [CI95 %: 2.07–56.71]. VaM recurred earlier than VuM (3.12 months [CI95 %: 2.07–12.49] versus 17.72 [CI95 %: 3.58–56.71], p = 0.011). VaM had a higher risk of recurrence (HR = 5.64 [CI95 %: 2.01–15.82], p = 0.001) in multivariate analysis. Overall survival was 88.5 % at 1 year (100 % for VuM and 50 % for VaM), and 59.4 % at 3 years (69.3 % for VuM and 25 % for VaM). Women with VaM died earlier: median specific death occurrence of 8.76 months [CI95 %: 6.54–24.72] versus 39.61 [CI95 %: 21.89–209.21], p = 0.013 (HR = 5.08 [CI95 %: 1.39–18.60], p = 0.014). A lesion size ≥3 cm was associated with an increased risk of mortality (HR = 8.45 [CI95 %: 1.60–44.52], p = 0.012). In multivariate analysis, vaginal location remained an independent and predictive variable of a higher risk of specific death (HR = 8.56 [CI95 %: 1.95–37.64], p = 0.005). Conclusion A vaginal location of MM is associated with a poorer prognosis than a vulvar location.