The large cell transformation of mycosis fungoides (MF-LCT) is a phenomenon observed in the advanced stages of mycosis fungoides (MF), which is the most common primary cutaneous lymphoma. The diagnostic criteria of MF-LCT are a minimum of 25% of large cells or a formation of microscopic nodules of them in the histological examination of skin samples. The clinical outcomes for MF-LCT are poor, as less than 20% of patients survive 5 years after diagnosis, but the expression of the CD30 antigen is generally considered to be associated with a better prognosis. We present a case of a patient with the diagnosis of MF with LCT, with an ulcerated tumor lesion approximately 30 × 20 cm in size on the right lateral abdominal wall. Brentuximab vedotin (BV) treatment was started due to the presence of the CD30 antigen, with a quick and impressive regression of the cutaneous lesion and tumor mass and good treatment tolerance. After follow-up of 20 months, patient remains in complete remission. A schedule of treatment for MF-LCT is directed mainly by the clinical stage of the disease and the comorbidities; the more severe clinical course of the disease requires systemic treatment. If at least 5% of the cells found in the skin lesions biopsy sample express the CD30 antigen, a beneficial effect of BV treatment could be expected. It may seem that the use of BV is one of the optimal therapeutic options in patients with advanced MF-LCT showing expression of CD30.