PURPOSE: Advanced cutaneous T-cell lymphoma (CTCL) is a hard-to-treat condition. Complete response is rare even with polychemotherapy. The use of liposomal formulation anti-cancer drugs can improve the efficacy and the risk-benefit ratio. Liposomal doxorubicin was shown to be effective as a second-line treatment in CTCL. There is no data available on another classical anthracycline, daunorubicin, when given in liposomal formulation as a monotherapy. METHODS: Monotherapy with liposomal-encapsulated daunorubicin (DNX) was given as a monotherapy once a month at 20 mg/m(2) three times to achieve a clinical response. In the case of limited response the drug was given once every 3 weeks and a dose increase was performed. Three patients were treated. RESULTS: A complete response was achieved in one patient (dosage 20 mg/m(2 )once per month). Two other patients achieved a partial response. The final outcome was disease-free survival of more than 10 months in the patient with a complete response and survival of >8 months and 6 months in those with a partial response. Adverse effects were grade 4 anemia in one patient, lymphopenia grade 2 with grade 1 anemia, and grade 1 lymphopenia in the other patients. CONCLUSION: This is the first report on DNX monotherapy in CTCL. In a small group of three patients a response rate of 100% was achieved with one complete response. DNX seems to be another option in advanced cases of CTCL.