Among 139 patients with medullary thyroid cancer (MTC) treated at the Royal Marsden Hospital between 1957-1998, 51 had persistently elevated calcitonin levels after initial surgery in the absence of clinically or radiologically demonstrable residual disease. Of these, 24 were treated with radiotherapy because of advanced local disease at presentation; this resulted in normalization of calcitonin in only 1 patient, although 10 remained free of clinical recurrence. Surveillance alone was used in the remaining 27 patients, of whom 8 (30%) remained free of overt disease. Local relapse rate was significantly lower after radiotherapy (29% vs. 59%) but there was no significant difference in 10-year survival between the two groups (72% vs. 60%). In view of this favorable long-term survival of patients with elevated calcitonin on observation, we cannot recommend the routine use of radiotherapy. However, it does appear to have a role in those presenting with more advanced disease to reduce the incidence of loco-regional relapse.