Desmoid tumors, also referred to as infantile fibromatosis, overlap with infantile myofibromatosis. A combination of standard agents that has been successfully used to treat desmoid tumors in infants is vinblastine and methotrexate (24). As opposed to cyclophosphamide-based regimens, this combination has the distinct advantages of few acute side effects and no known long-term toxicities, such as infertility or second malignancy. These agents have been used for over 30 years to treat infant and childhood malignancies. Over the last five years, methotrexate and vinblastine have been used to treat 9 children with recurrent desmoid tumor, a lesion similar although not identical to the abnormality present in patients with pulmonary vein stenosis. This regimen had minimal acute toxicity limited to mild to moderate nausea (which is easily controlled with anti-emetic therapy), minimal alopecia, mild hepatic inflammation, and mild myelosuppression. An addition advantage is that these drugs do not interfere with listing for lung transplantation, an important factor in the overall treatment options for this patient population. Instead of high-dose administration of chemotherapy (that catches only those cells in cycle at the time of administration), the low-dose chronic weekly administration continues to catch proliferating cells as they continually come into cycle. This may explain why the only other trial of chemotherapy (with high-dose cytoxan) was unsuccessful. Of the 9 children with desmoid lesions who received vinblastine and methotrexate therapy, four patients were treated for 18 months or longer. At the time of the last report, no patient had progressive disease during therapy. Two children had radiographically stable disease 1 and 2 years after treatment. Two children had stable disease for 1 and 2 years after treatment and then had disease progression. Thus, this drug combination is well-tolerated, has minimal side effects, and has demonstrated clinical activity against a closely related type of lesion.