• Patients will receive thalidomide(200mg) orally once daily for two weeks. If after two weeks of thalidomide, the patient is doing well the dose of thalidomide will increase (400mg) and they will remain on it for up to 50 additional weeks. The length of time a patient is on thalidomide will depend upon how they are responding to therapy.
• During the second week of the study patients will also begin receiving rituximab intravenously once weekly for 4 weeks, which may then be repeated 8 weeks later depending upon the response.
• A determination of how the patient is responding will be made based on testing conducted at 12 weeks. This testing includes blood tests and possibly a bone marrow biopsy. If it is determined that the disease is not progressing, patients will begin a second phase of treatment which includes 4 additional weekly infusions of rituximab and the continuation of oral thalidomide.
• If it is determined at the 12-week evaluation, or at any time thereafter, that the disease has progressed (by studying serum IgM levels, bone marrow involvement, tumor cells, and/or development of new signs and symptoms) then the patient will be removed from the study.
• Periodic examinations and tests will be done to determine how the patient is doing, what response and side effects (if any) the patient may be having from the study drugs. If patient is responding to therapy then they will remain on this study and followed for a period of two years.
• Bone marrow biopsies and aspirations will be obtained at 3-6 month intervals extending for 2 years following the last treatment.

Inclusion Criteria:

• Clinicopathological diagnosis of Waldenstrom''''s macroglobulinemia requiring therapy
• Baseline staging requirements
• ANC > 500/uL
• PLT > 25,000/uL
• Serum creatinine < 2.5mg/dL
• Total bilirubin and SGOT < 2.5 X ULN
• Greater than 18 years of age
• Life expectancy of 3 months or greater
• ECOG status performance of 0-2

Exclusion Criteria:

• Chemotherapy, steroid therapy, or radiation therapy within 30 days of study entry
• Pregnant or lactating women
• Serious co-morbid disease
• Uncontrolled bacterial, fungal or viral infection
• Active second malignancy