Inclusion Criteria:

1. Understand and voluntarily sign an informed consent form.
2. Age >=18 years at the time of signing the informed consent form.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Newly diagnosed or relapsed AL amyloidosis.
5. Biopsy-proven amyloidosis with evidence of an underlying plasma cell dyscrasia (abnormal clonal dominance of plasma cells in the bone marrow, and/or detection of a monoclonal gammopathy by immunofixation electrophoresis of serum and/or urine, and/or an abnormal serum free light chain or ratio, or AL fibrils seen on biopsy).
6. Measurable disease, defined by an abnormal serum free light chain or monoclonal protein by immunofixation, proteinuria >= 0.5g/day, cardiac involvement with interventricular septal thickness >= 15mm, or hepatomegaly in the absence of congestive heart failure with elevated alkaline phosphatase.
7. All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study.
8. ECOG performance status of <= 3 at study entry (see Appendix II).

9. Laboratory test results within these ranges:

   • Absolute neutrophil count >= 1.0 x 10^9/L.
   • Platelet count >= 75 x 10^9/L
   • Creatinine clearance >= 15mL/minute (calculated by MDRD Equation or Cockcroft-Gault, or measured by 24-hour urine collection).
   • Total bilirubin <= 2-fold upper limits of normal.
10. Disease free of prior malignancies (excluding multiple myeloma) for >= 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
11. All study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist.
12. Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. See Appendix: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.
13. Able to take aspirin (81 mg) daily or alternative (see below) as prophylactic anticoagulation. Patients intolerant to aspirin may use coumadin or low molecular weight heparin. Patients requiring full dose anticoagulation for a prior thrombosis can take low molecular weight heparin (preferred) or coumadin instead of aspirin.

Exclusion Criteria:

1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
2. Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
3. Use of any other experimental drug or therapy within 28 days of baseline.
4. Known hypersensitivity to thalidomide.
5. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
6. Any prior use of lenalidomide.
7. Concurrent use of other anti-cancer agents or treatments.
8. Known positive for HIV.