Inclusion Criteria:

1. Understand and voluntarily sign an informed consent form.
2. Age greater than or equla to18 years at the time of signing the informed consent form
3. Able to adhere to the study visit schedule and other protocol requirements
4. Biopsy-proven non-Hodgkin’s lymphoma
5. Aggressive lymphoma, the following histologies are acceptable: a.Follicular center lymphoma, grade 3, b. Diffuse large cell, c.Mantle cell, d.Transformed
6. Relapsed or refractory to previous therapy for lymphoma. Subjects must have received at least one prior treatment regimen such as radiation, immunotherapy, chemotherapy, OR radioimmunotherapy, and be ineligible or unwilling to undergo an autologous stem cell transplant. There is no limit on the number of prior therapies.
7. Subjects must have measurable disease on cross sectional imaging that is at least 2 cm in the longest diameter. Be ineligible or unwilling to undergo a stem cell transplant.
8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2 (see Appendix II).
9. Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test within 7 days of starting study drug. In addition, sexually active WCBP must agree to use adequate contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on study drug.

Exclusion Criteria:

1. Any of the following laboratory abnormalities:

   1. Absolute neutrophil count (ANC) <1,500 cells/mm3 (1.5 x 109/L)
   2. Platelet count <100,000/mm3 (100 x 109/L)
   3. Serum creatinine >2.5 mg/dL (221 mmol/L)
   4. Serum SGOT/AST or SGPT/ALT >5.0 x upper limit of normal (ULN)
   5. Serum total bilirubin >2.0 mg/dL (34 mmol/L)
2. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
3. All subjects with CNS disease with the exception of those subjects whose CNS disease has been treated with chemotherapy, radiotherapy or surgery and remains asymptomatic, with no active CNS disease, as shown by lumbar puncture, CT scan or MRI, for at least 6 months.
4. Prior history of malignancies other than non-Hodgkin’s lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for > or equal to 1 year
5. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
6. Known positive for HIV
7. Pregnant or lactating females
8. Prior > or equal to grade 3 (Appendix III: NCI CTCAE) allergic reaction/hypersensitivity to thalidomide
9. Prior > or equal to grade 3 (Appendix III: NCI CTCAE) rash or any desquamating (blistering) rash while taking thalidomide
10. Prior use of lenalidomide
11. Use of any standard or experimental anti-cancer drug therapy within 28 days of day 1 of study drug therapy
12. Known active Hepatitis C