HYPOTHESIS: A tumor-negative sentinel node (SN) does not eliminate the chance of melanoma recurrence. Patterns of metastasis can be identified and characterized in patients with tumor-negative SNs. DESIGN: Retrospective review. SETTING: Melanoma referral center. PATIENTS: Patients who underwent lymphatic mapping and sentinel lymphadenectomy between 1995 and 2002 and whose SNs were negative for metastasis by hematoxylin-eosin and immunohistochemistry staining were included in the study. The SN specimens from patients with recurrent disease were reexamined for missed metastasis. MAIN OUTCOME MEASURES: Differences in survival related to sites of recurrence and the rate of false-negative histopathologic SN diagnosis were determined. RESULTS: At a median follow-up of 36.7 months, 69 (8.9%) of 773 patients with tumor-negative SNs had recurrent disease. Three-year survival after first recurrence was 17.1% in the 37 patients with distant recurrence, 48.7% in the 19 patients with local or in-transit recurrence, and 63.5% in the 13 patients with regional basin recurrence; the difference in survival between patients with local or regional and distant recurrences was statistically significant (P<.001). Histopathologic reexamination of SNs from the 69 patients identified 9 patients with false-negative SNs; 2 of these had same-basin recurrences. CONCLUSIONS: The SN is a valuable prognostic indicator because only 8.9% of patients with tumor-negative SNs will develop recurrence. The low incidence (1.7%) of regional basin recurrence in patients with negative SNs supports the accuracy of our current method of lymphatic mapping and sentinel lymphadenectomy to identify occult regional nodal basin metastasis.