BACKGROUNDMucosa‐associated lymphoid tissue (MALT) lymphoma is a specific clinicopathologic entity with gastric and nongastrointestinal site involvement. The authors reported the clinical outcome of patients with Stage IE nongastrointestinal MALT lymphoma treated with a frontline fludarabine‐containing regimen or with a regimen containing cyclophosphamide, vincristine, and prednisone (CVP).METHODSBetween 1998 and 2001, 31 patients with Stage IE disease were referred to the Seràgnoli Institute of Hematology and Medical Oncology at the University of Bologna (Bologna, Italy). Presenting sites included periorbital soft tissue (n = 8), lung (n = 5), skin (n = 5), salivary glands (n = 5), lacrimal glands (n = 5), and thyroid (n = 3). Twenty patients were treated with fludarabine and mitoxantrone (FM), and 11 were treated with the CVP regimen. The median follow‐up was 3 years.RESULTSAll patients achieved complete responses (CR). Four patients, all treated with CVP, experienced disease recurrence and then achieved a second CR after FM salvage treatment. No tumor recurrence was observed in patients with thyroid, lacrimal gland, or pulmonary lymphoma. The projected 5‐year overall survival and disease‐free survival rates were 100% and 85%, respectively.CONCLUSIONSThe fludarabine‐containing FM regimen provided a relatively effective frontline (or salvage) treatment option for patients with nongastrointestinal Stage IE MALT lymphoma and probably was superior to CVP in terms of efficacy. Cancer 2004. © 2004 American Cancer Society.