Dysesthesias of the lower limbs are a common complaint of patients and may be indicative of peripheral neuropathy. Here we investigated the prevalence and type of neuropathy in patients presenting with this complaint and compared the diagnostic performance of different diagnostic modalities. Forty-two patients were recruited prospectively and underwent a clinical examination, nerve conduction studies, quantitative sensory testing (QST), and skin biopsy at the dorsum of the foot. All patients had a correlate for their dysesthesias in at least one diagnostic modality. Most patients (>90%) had signs of small fiber loss or dysfunction. In about half of all patients large fibers were also affected. Nerve conduction studies were abnormal in 23/42 patients (54.8%). Cold or warm detection thresholds in QST were abnormal in 15/42 (35.7%) patients. Decreased intraepidermal nerve fiber density (IENFD) was found in 37 patients (88.1%), including some patients with normal QST findings. Nearly all patients with pathological QST had a reduced IENFD, indicating a high positive predictive value (93%) of QST in screening for reduced IENFD as correlate for neuropathy. Therefore in all patients with lower limb dysesthesias of unknown origin, the non-invasive methods of NCS and QST should be used and potentially complemented by skin biopsy.