A Phase II study of teniposide (VM26) in cutaneous T-cell lymphoma (CTCL) was performed in 15 patients affected by stage III, IV according to TNM (mycosis fungoides or Sézary syndrome). All patients were pretreated, and VM26 was administered at a dose of 100 mg/m2 weekly for at least 3 weeks. Objective responses were observed in 40% of the patients, with two complete responses lasting 26 and 46 months. The drug was well tolerated in elderly patients and deserves further evaluation either for inclusion in first-line combination regimens or for palliative treatment in heavily pretreated or elderly patients.