Clinical symptoms can indicate peripheral neuropathy, but an exact diagnosis requires a combination of medical history, medical tests, and possibly a process of exclusion. Certain symptoms can suggest a diagnosis, but more information is commonly needed. For example, painful, burning feet may be a symptom of alcohol abuse, diabetes, HIV infection, or an underlying malignant tumor, among other causes. Without further details, effective treatment would be difficult.

During a physical examination, an individual is asked to describe the symptoms very carefully. Detailed information about the location, nature, and duration of symptoms can help exclude some causes or even pinpoint the actual problem. The person's medical history may also provide clues as to the cause, because certain diseases and medications are linked to specific peripheral neuropathies. A medical history should also include information about diseases that run in the family, because some peripheral neuropathies are genetically linked. Information about hobbies, recreational activities, alcohol consumption, and work place activities can uncover possible injuries or exposures to poisonous substances.

The physical examination also includes blood tests, such as those that check levels of glucose and creatinine to detect diabetes and kidney problems, respectively. A blood count is also done to determine levels of different blood cell types. Iron, vitamin B12, and other factors may be measured as well, to rule out malnutrition. More specific tests, such as an assay for heavy metals or poisonous substances, or tests to detect vasculitis, are not typically done unless there is reason to suspect a particular cause.

An individual with neuropathy may be sent to a doctor that specializes in nervous system disorders (neurologist). By considering the results of the physical examination and observations of the referring doctor, the neurologist may be able to narrow down the possible diagnoses. Additional tests, such as nerve conduction studies and electromyography, which tests muscle reactions, can confirm that nerve damage has occurred and may also be able to indicate the nature of the damage. For example, some neuropathies are characterized by destruction of the myelin. This type of damage is shown by slowed nerve conduction. If the axon itself has suffered damage, the nerve conduction may be slowed, but it will also be diminished in strength. Electromyography adds further information by measuring nerve conduction and muscle response, which determines whether the symptoms are due to a neuropathy or to a muscle disorder.

In approximately 10% of peripheral neuropathy cases, a nerve biopsy may be helpful. In this test, a small part of the nerve is surgically removed and examined under a microscope. This procedure is usually the most helpful in confirming a suspected diagnosis, rather than as a diagnostic procedure by itself.