The Italian CTS Study Group performed a wide multicentric and multiparametric study to quantify the increase of electrodiagnostic sensitivity using an extended neurophysiological protocol and particularly segmental and comparative tests. The study also evaluated the clinical features of carpal tunnel syndrome (CTS) diagnosed by these tests, using validated physician- and patient-oriented measurements. The study group was composed of 740 patients for a total of 1123 idiopathic CTS hands. Overall, the sensitivity of standard tests (median digit-wrist sensory conduction velocity and wrist-thenar distal motor latency) was 83.5%. Comparative/segmental tests disclosed abnormal findings in a further 11.4% of cases, providing CTS electrodiagnosis in about 7 of 10 "standard negative" cases. The overall sensitivity of the electrodiagnostic protocol was 94.9%. The CTS population diagnosed by segmental/comparative tests had a clinical picture characterized by a high percentage of pain, and severe discomfort but no limitation in functional daily activity. Our data confirm the usefulness of a complete neurophysiological assessment by using segmental/comparative tests when standard tests yield normal results.