Despite their benign histological appearance and the current literature composed primarily of case reports with favorable outcomes, ganglion cysts involving peripheral nerves (GCPNs) can cause permanent neurological deficits. The authors present a 27-year Louisiana State University Medical Center (LSUMC) experience with the surgical management of GCPNs. From 1968 to 1995, 27 patients were surgically treated for 27 cysts that involved nerves at nine locations. Cysts of the peroneal nerve were the most common, comprising 52% of the cases. Motor deficit, pain, and sensory changes were present in 83%, 78%, and 48% of cases, respectively. A history of acute trauma was noted in 22%. The mean follow-up duration in these cases was 61 months. Motor recovery was good in only 58% of cases and was related to the severity of the preoperative motor deficit. Pain resolved or was significantly improved in 89% of cases. Five patients underwent nine procedures before referral to LSUMC for treatment of recurrence of their ganglion cysts. None of these patients suffered recurrence after undergoing surgery at LSUMC. However, four additional patients (17%) experienced a total of six recurrences after undergoing their initial procedure. The mean time to recurrence for the patient group as a whole was 16 months. On the basis of their experience, the authors conclude that GCPNs can behave in an aggressive fashion. Patients should be counseled preoperatively about the potential for limited motor recovery and a significant chance for recurrence.