Background: Mycosis fungoides (MF) is a cutaneous T cell lymphoma. There are only palliative treatments in advanced stages with no cure. Most chemotherapy regimens have temporary effects with various side effects. Objective: The objective of this study was to assess the efficacy of a new chemotherapy regimens in advanced stages of MF. This regimens takes advantage of synergistic effect of methotrexate and fluorouracil and also uses leucovorin to reduce side effects of methotrexate. Patients and Methods: Five patients with advanced stages of MF (Stage IIB and higher) were treated with several courses of this chemotherapy regimens in a quasi experimental study. Results: Four patients responded partially one responded completely to this regimen but all of them relapsed after tapering the treatment. All of them tolerated the drugs well and no serious side effects were observed. Tumoral lesions showed better response. Conclusion: Although this chemotherapy regimen, similar to other regimens, only had temporary and palliative effects, it was tolerated well without serious side effects.