Initial complaints in PSP are typically vague and an early diagnosis is always difficult. The primary complaints fall into these categories: 1) symptoms of disequilibrium, such as unsteady walking or abrupt and unexplained falls without loss of consciousness; 2) visual complaints, including blurred vision, difficulties in looking up or down, double vision, light sensitivity, burning eyes, or other eye trouble; 3) slurred speech; and 4) various mental complaints such as slowness of thought, impaired memory, personality changes, and changes in mood.

PSP is often misdiagnosed because some of its symptoms are very much like those of Parkinson's disease, Alzheimer's disease, and more rare neurodegenerative disorders, such as Creutzfeldt-Jakob disease. In fact, PSP is most often misdiagnosed as Parkinson's disease early in the course of the illness. Memory problems and personality changes may also lead a physician to mistake PSP for depression, or even attribute symptoms to some form of dementia. The key to diagnosing PSP is identifying early gait instability and difficulty moving the eyes, the hallmark of the disease, as well as ruling out other similar disorders, some of which are treatable.