BACKGROUND: Lymphatic mapping and sentinel lymph node (SLN) biopsy are new techniques used in the surgical treatment of patients with malignant melanoma. These procedures have the potential to change the surgical treatment of the disease to provide a more rational approach to adjuvant therapy. METHODS: A prospective database of melanoma patients undergoing lymphatic mapping and SLN biopsy was reviewed to identify prognostic factors for overall and disease-free survival in this patient population. RESULTS: Five-year overall and disease-free survival was 92.3% and 79.0%, with a median follow-up of 17 months. The number of histologically positive SLNs was the most powerful predictor of overall and disease-free survival. Patients with no histologically positive SLNs had a five-year overall and disease-free survival of 97.9% and 93.3%, respectively. Tumor ulceration and Clark level greater than or equal to III were the significant prognostic factors for survival. CONCLUSIONS: The use of lymphatic mapping and SLN biopsy effectively stages patients with primary cutaneous melanoma. Additionally, the presence of histologically positive SLNs is the most powerful indicator of overall and disease-free survival for these patients.