Electrochemotherapy (ECT) has emerged as a complementary treatment for superficial metastases. Fifty-two consecutive patients with different cancer histotypes, mainly melanoma and breast cancer, with disease unsuitable for conventional treatments underwent bleomycin-based ECT for cutaneous and subcutaneous metastases. Toxicity, local response, response duration, and the impact on quality of life were evaluated. A total of 608 tumor nodules were treated (mean, 12 per patient), with 27% of patients affected by nodules >3 cm in size. Treatment was tolerated well, especially under general sedation. An objective response was obtained in 50 (96%) of 52 patients 1 month after the first application. Twenty-two patients underwent a second treatment (because of partial response or the appearance of new lesions). Partial response at first ECT achieved a response consolidation at second application: 80% complete response, 20% partial response. Some patients underwent up to five treatments because of new lesions, but maintained superficial tumor control. After a mean follow-up of 9 (range, 2-21) months, only two patients experienced relapse in the treatment field. Through a nonvalidated eight-item questionnaire (assessing wound healing and bleeding, aesthetic impairment, daily activities, social relations, pain, treatment satisfaction, acceptance of retreatment), most patients reported a benefit in local disease-related complaints and in activity of daily living. In a palliative setting, ECT proved to be safe, effective in all tumors treated, and useful in preserving patients' quality of life. This benefit, although preliminary, deserves further assessment after a formal validation of the dedicated questionnaire.