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. Recurrent or metastatic squamous cell or undifferentiated carcinoma of the head and
neck that is not amenable to curative therapy. Patients who are candidates for local
or locoregional therapy should not be deprived of proven beneficial palliative
therapies.

5. All previous cancer therapy, including radiation, hormonal therapy, EGFR inhibitors,
and surgery, must have been discontinued at least 4 weeks prior to treatment in this
study.

6. ECOG performance status of 0-1 at study entry.

7. Laboratory test results within these ranges:

- Absolute neutrophil count to ≥ 1000/mm³

- Platelet count ≥ 100,000/mm³

- Calculated creatinine clearance ≥ 50ml/min by Cockcroft-Gault estimation

- Total bilirubin < 1.5 x ULN

- AST (SGOT) and ALT (SGPT) < 3 x ULN or < 5 x ULN if hepatic metastases are
present.

8. Disease free of prior malignancies 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. Patients with malignancies diagnosed less than 3 years prior to study
entry are eligible if the first cancer was no greater than stage I and did not recur.
Patients with malignancies diagnosed less than 3 years prior to study entry must have
the diagnosis of recurrent or metastatic squamous cell carcinoma of the head and neck
confirmed pathologically.

9. All study participants must be registered into the mandatory RevAssist® program, and
be willing and able to comply with the requirements of RevAssist®.

10. 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.

11. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients
intolerant to ASA may use warfarin or low molecular weight heparin).

12. Measurable disease, defined as at least one lesion that can be accurately measured in
at least one dimension (longest diameter to be recorded), with minimum lesion size ≥
2 cm on conventional measurement techniques or ≥ 1 cm on spiral computed tomography
(CT) scan. Lesions that can be measured clinically must be at least 1 cm in greatest
dimension by caliper measurement.

Exclusion Criteria:

1. Primary head and neck carcinomas of the salivary gland, skin, or thyroid regardless
of pathology

2. Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent form.

3. Pregnant or breast feeding females. (Lactating females must agree not to breast feed
while taking lenalidomide).

4. 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.

5. Use of any other experimental drug or therapy within 28 days of baseline.

6. Prior therapy with lenalidomide for squamous cell carcinoma of the head and neck

7. Known hypersensitivity to thalidomide.

8. The development of erythema nodosum if characterized by a desquamating rash while
taking thalidomide or similar drugs.

9. Concurrent use of other anti-cancer agents or treatments.

10. Known positive for HIV or infectious hepatitis, type B or C.