The application of electric pulses to skin tumour nodules enhances the antitumour effectiveness of cisplatin. This treatment approach, known as electrochemotherapy, was employed in the treatment of skin metastases and lymph node metastases in malignant melanoma patients. Electric pulses were applied to tumour nodules in order to potentiate locally the antitumour effectiveness of systemic cisplatin-based chemoimmunotherapy. The study included nine malignant melanoma patients with skin metastases and metastases in lymph nodes not amenable to surgery, undergoing cisplatin-based chemoimmunotherapy. The antitumour effectiveness of the chemoimmunotherapy was compared with the antitumour effectiveness of electrochemotherapy, i.e. application of electric pulses to tumour nodules together with cisplatin-based chemoimmunotherapy. Application of electric pulses to the 27 skin tumour nodules potentiated locally the antitumour effectiveness of cisplatin. Four weeks after the treatment, 48% of the tumour nodules had an objective response (OR), compared with 22% of the 18 tumour nodules treated with cisplatin-based chemoimmunotherapy alone. Furthermore, the median time to progression was longer in the electrochemotherapy-treated nodules (21 weeks) than in the chemoimmunotherapy-treated nodules (4 weeks). This study shows that application of electric pulses to malignant melanoma tumour nodules can potentiate the antitumour effectiveness of cisplatin in patients undergoing systemic cisplatin-based chemoimmunotherapy. Therefore, electrochemotherapy may be used as an adjunct to systemic ongoing cisplatin treatment, predominantly in patients in whom antitumour effectiveness needs to be potentiated locally.