Five organically impaired and depressed head and neck cancer patients had a marked therapeutic response to methylphenidate (MPD). There was a rapid remission of depressive and cognitive dysfunctions without adverse side effects. The relationship of cognitive, behavioral, and affective symptoms to brain function is discussed. To rule out treatable cognitive and affective disorders, neurobehavioral assessment of the depressed head and neck cancer patient is stressed, and diagnostic and treatment guidelines are given. The results suggest that further evaluation is warranted of the use of MPD in treating seriously ill cancer patients who have either compromised brain function or depression.