On the basis of personal experience and a review of the literature, the authors have evaluated the results obtained with hyperthermic antiblastic perfusion (HAP) for the treatment of stage II, III and IIIAB limb melanoma. The evaluation showed that today HAP may be considered a safe and effective treatment, with a major complication rate ranging between 1% and 4%. In terms of tumor response, locoregional control and survival, this treatment has provided better results than other regional chemotherapeutic modalities and undoubtedly better results than those obtained with conventional, even radical, surgery. The multiparametric analysis showed that, of the treatment-related prognostic factors, the minimum tumor temperature influenced the percentage of complete response (CR) to the greatest extent (P < 0.03), with a positive trend also with regard to the dosage of the antiblastic drug employed (P < 0.08). In turn, the complete response rate was a determinant as far as locoregional control (75.3%; P < 0.0009) and disease-free (51.4%; P < 0.009) and overall survival (63.2%; P < 0.009) rates were concerned. Of the tumor-related prognostic factors, the number of lesions (P < 0.0014), sex (P < 0.04), and the number of disease recurrences (P < 0.01) appear to influence overall survival.