Inclusion Criteria:

• Patients with potentially resectable pancreatic cancer (including ampullary cancer), prior to or after surgery will be accrued to this study.
• Patients who sign consent prior to surgery must have appropriate diagnostic imaging and be evaluated by one of the surgical co-investigators as having resectable disease, and probable pancreatic adenocarcinoma.
• Patients, who sign consent after surgery, must have adenocarcinoma of the pancreas with negative surgical margins.
• Adjuvant therapy should start within 10 weeks of surgery
• Age 18 years or older
• ECOG performance status of 0 - 1 (see Appendix A)
• Ability to take oral medications without difficulty
• Adequate bone marrow function as evidenced by an absolute neutrophil content (ANC) > 1500/mL and platelet count > 100,000/mL
• Adequate renal function as evidenced by serum creatinine within institutional limits or creatinine clearance > 50 ml/minute if above upper institutional limits (ULN)
• Adequate hepatic function as evidenced by ALT and total bilirubin within 2 times ULN.
• Provision of written informed consent.
• Men and women of childbearing potential must be willing to practice acceptable methods of birth control to prevent pregnancy.

Exclusion Criteria:

• Positive margins on post operative surgical specimen or evidence of metastatic disease (positive retroperitoneal margin is allowed)
• Biliary tree cancers are not allowed (Note: Ampullary cancer allowed).
• Known severe hypersensitivity to erlotinib or any of the excipients of these products
• Any prior treatment with radiation therapy or chemotherapy or vaccines for pancreatic cancer.
• Other coexisting malignancies or malignancies diagnosed within the last 3 years, with the exception of basal cell carcinoma or squamous cell carcinoma of the skin or cervical cancer in situ.
• Concomitant use of phenytoin, carbamazepine, barbiturates, rifampicin, phenobarbital, or St. John's Wort. Other agents which inhibit CYP3A4 may be used with caution (Appendix B)
• Treatment with a non-approved or investigational drug prior to treatment.
• Incomplete healing from previous oncologic or other major surgery.
• Pregnancy or breast feeding (women of childbearing potential).
• As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease).
• Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the trial.