Objective: The site of treatment failure in patients with recurrent well-differentiated thyroid carcinoma (WDTC) has implications for both the mode of salvage therapy and disease-specific prognosis. The objective of this study was to evaluate the prognostic significance of the site of failure in patients with recurrent WDTC. Design: Patients with recurrent thyroid cancer were identified retrospectively from 1963 to 2000. Setting: Data were retrieved from the thyroid cancer database at the Department of Otolaryngology-Head and Neck Surgery, Mount Sinai Hospital, Toronto (1963-2000). Methods: Patients were placed into four different groups according to their site of recurrence: group 1, local recurrence; group 2, regional recurrence; group 3, distant recurrence; and group 4, unspecified recurrence. Patient, turnout, and treatment data were collected and compared. The Kaplan-Meier method was used to calculate survival data, and curves were compared using the log rank test. Main Outcome Measures: Outcome included alive, no disease; alive with disease; dead, no disease; and dead of disease. Results: Seventy-three patients (21 male, 52 female; median age 44 years, range 18-84 years) were eligible for inclusion in this study. Relevant data were divided according to group 1, 22 patients; group 2, 24 patients; group 3, 13 patients; and group 4, 14 patients. The groups were comparable in terms of primary turnout and treatment factors. The actuarial disease-specific survival rate after salvage therapy was less significant in patients who developed a distant recurrence versus a local recurrence, a regional recurrence, or an unspecified recurrence (ie, 66% vs 95%, 88%, and 92%, respectively; p = .06). Conclusions: Patients with distant recurrences have a poor prognosis, with a significant reduction in the actuarial disease-specific survival rate.