We describe herein what is to our knowledge the first reported case of an invasive cutaneous metastasis with unknown primary, electively treated solely with electrochemotherapy. We describe a female patient with a large, invasive and painful lesion in her hypogastric region, extending up to the pubic area. The cutaneous biopsy and instrumental and laboratory analyses, all failed to reveal the primary site. A final diagnosis of cutaneous metastasis with unknown primary was made and treatment was performed with electrochemotherapy. Our case highlights the importance of interdisciplinary choices in clinical practice to cope with the lack of a primary site and to improve quality of life, since no standardized therapy exists for these classes of patients.