--is currently the "gold standard" for determining the density and condition of the small nerve fibers that subsume the sensations of pain and temperature. Often, in cases of small-fiber neuropathic symptoms, it may be the only abnormal test, but a "normal" skin biopsy may not rule out a problem, as the normal ranges are established statistically--for small fiber density, these are set at the 5 and 95 percentiles as established by the MacArthur protocols from Johns Hopkins medical center--and one may have damage or reduction in density and not fall outside the protocols (this is one reason the condition of the nerves is also evaluated).

In order to check for length-dependent or "die-back" processes, samples are normally taken right above the ankle, the upper thigh, and the upper arm, but samples can also be taken from the lower arm, the face, or theoretically anywhere there is hairy skin.