The aim of this study was to present the epidemiological, clinicopathological, and treatment characteristics of patients diagnosed and treated in a tertiary referral center and to analyze independent factors associated with these characteristics. In this cohort study, epidemiological, clinicopathological, and treatment characteristics of 1461 consecutive melanoma patients diagnosed and treated in a tertiary referral center in 1987–2015 were prospectively collected in a registry. All patients underwent resection of their melanoma lesion. Multiple logistic regression analysis was used to examine independent correlations between characteristics. Internal validation of these correlations was performed by the bootstrap method. The median age of the patients was 53 years. Female sex had a slight predominance, whereas the majority were of Southern European origin. Superficial spreading melanoma was associated with younger age (P<0.001), whereas the nodular melanoma histological subtype was associated independently with indoor occupation (P=0.021) and diagnosis in the years 2004–2015 (P=0.002). Melanomas with Breslow thickness above 1.0 mm were associated with skin type III–IV (P=0.021) and diagnosis in the years 1987–2003 (P=0.046). In addition, histological ulceration was associated with older age (P=0.004) and diagnosis in the years 1987–2003 (P<0.001), whereas histological regression was associated independently with older age (P=0.001). This study presented independent associations between epidemiological, histopathological, and treatment characteristics, which might help to better understand melanoma disease and treatment practices in Southern Europe.