Inclusion Criteria:

- Patients must have microscopically confirmed epidermoid/squamous cell carcinoma
(HNSCC) of the oral cavity, pharynx, larynx, paranasal sinus, or head/neck squamous
cell carcinoma unknown primary.

- Patients must have recurrent or metastatic disease which is not amenable to
curative-intent therapy with surgery or radiation.

- No more than 2 prior cytotoxic therapies in the recurrent or metastatic disease
setting are permitted.

- Patients must be at least 18 years of age.

- Karnofsky Performance status must be ≥ 70%.

- Disease must be measurable by RECIST criteria.

- At least 4 weeks must have elapsed from previous radiation therapy. Patient must have
recovered from the acute toxic effects of treatment prior to study enrollment.

- Prior radiation therapy to ≤ 25% of bone marrow is allowed. Prior radiation to the
whole pelvis and/or brain is not allowed.

- Adequate organ function

- Patients of childbearing potential must have a negative test for pregnancy at time of
enrollment based on a urine or serum pregnancy test. Patients must agree to use a
reliable method of birth control during and for 3 months following the last dose of
study drug.

- Patient must reside in geographic proximity to MSKCC for adequate follow-up during
treatment, per investigator discretion.

- Patients must sign an informed consent document.

Exclusion Criteria:

- Previous exposure to pemetrexed (Alimta) or gemcitabine (Gemzar).

- Pregnancy or breast-feeding.

- Serious concomitant systemic disorders (for example, active infection) that, in the
opinion of the investigator, would compromise the safety of the patient or compromise
the patient's ability to complete the study.

- History of any brain metastases.

- Inability or unwillingness to take folic acid, vitamin B12 supplementation, or
dexamethasone.

- Patients will be excluded if they will be unable to hold use of nonsteroidal
antiinflammatory agents (NSAIDS) with short elimination half lives