Inclusion Criteria:

1. Biopsy-proven recurrent squamous cell carcinoma of the head and neck
2. Stage 4 disease, either at initial presentation or at recurrence. Patients with metastatic disease at initial presentation must have received at least one prior course of cytotoxic chemotherapy.
3. Patients who present with metastatic disease should have received no more than one prior regimen of chemotherapy or biologic therapy to be eligible. Patients who initially received adjuvant or induction chemotherapy and then recurred may have received one additional cycle of chemotherapy or biologic therapy at the time of recurrence. Patients may have received any number of cycles of a particular regimen of chemotherapy.
4. Patients must have a life expectancy of at least 3 months
5. Biopsy of the recurrent lesion(s) is encouraged but not mandatory for enrollment.
6. Performance status grade 0-2.
7. Serum creatinine <= 1.5 mg/dL.
8. Serum transaminases and bilirubin <= 1.5 time normal.
9. Age >= 18 years.
10. White blood cell count >= 3,000; platelets >= 100,000; hemoglobin >= 9mg/dl.
11. Signed informed consent.
12. Women of childbearing potential must agree to utilize two methods of effective birth control, one barrier, one hormonal, or should abstain from sexual intercourse that could result in pregnancy. Contraceptive measures should be continued for at least one month after fenretinide administration has been discontinued.
13. It is recommended that male patients with female partners of childbearing potential use barrier contraception while on fenretinide.

Exclusion Criteria:

1. Pregnant women (women of childbearing potential must have a negative pregnancy test within 24 hours prior to enrollment in the study); women who are currently breast-feeding.
2. Grade 2 or greater peripheral neuropathy
3. Concurrent treatment with cytotoxic chemotherapy or radiation
4. Serious infection or other intercurrent illness requiring immediate therapy.
5. Inability to take oral medications, or other medical or social factors interfering with compliance.
6. Patients on high dose synthetic or natural Vitamin A derivatives (>= 10,000 per day).
7. Patients should not take any anti-oxidants such as Vitamin C or E.