Cancer, and the complications of cancer therapy, can present significant obstacles to the airman wishing to return to flying status. If found to be free of recurrent lymphoma and to be neurologically intact after completion of therapy, applicants can be considered for a time-limited medical certificate, provided that they are otherwise qualified. Long-term follow up of patients must include not only disease-free survival time, but also serial neuropsychometric evaluation and quality-of-life assessments. This case illustrates the aeromedical considerations and certification issues for a patient presenting with performance issues progressing to discreet neurological findings, culminating in the diagnosis and treatment of primary central nervous system (CNS) lymphoma.