The aim of this study was to determine independent clinical and pathological prognostic factors for overall and disease-free survival in Spanish melanoma patients. Eight hundred and twenty-three patients with localized melanoma and complete clinical and pathological information were evaluated. The age at diagnosis, gender, location, tumour thickness, invasion level, ulceration, histological subtype, inflammatory infiltrate, mitotic rate, vascular invasion, microscopic satellitosis, regression and cell type were all included. Univariate and multivariate Cox regression analyses were performed for overall and disease-free survival. Gender, histological subtype, tumour thickness, invasion level, ulceration, inflammatory infiltrate, microscopic satellitosis, vascular invasion and mitotic rate were related to overall and disease-free survival in univariate analysis. Age and location were only related to disease-free survival. Only tumour thickness, vascular invasion and gender exhibited independent significance for overall survival in multivariate analysis. For disease-free survival, tumour thickness, location, mitotic rate, vascular invasion and microscopic satellitosis were the sole independent factors. It can be concluded that the Breslow thickness remains the most significant prognostic factor for the survival of patients with localized cutaneous melanoma. Our results support the inclusion of microscopic satellitosis and vascular invasion in the current American Joint Committee on Cancer (AJCC) staging system, although further studies evaluating their separate influence are needed. Mitotic rate is confirmed as an objective and independent predictor of disease-free survival for melanoma patients that should be considered in further revisions of the mentioned staging system.