Background: The risk of lymph node involvement for cutaneous melanoma increases with tumor thickness - 5% for Breslow thickness ≤1mm and 34% for T4 or ulcerated lesions. SLNB is standard of care for cutaneous melanoma of Breslow thickness >1mm. Positive SLNB is followed by completion lymph node dissection (CLND) of the affected nodal basin. SLNB has a high negative predictive value (NPV) but false negative (FN) rates vary widely (3-12.5%). Methods: Data were collected on 3,600 patients (pts) who underwent SLNB for cutaneous melanoma from 1996 to 2012 using the UPCI Cancer Registry. Cancer registry records were reviewed for primary tumor characteristics, demographic details, and outcomes. The influence of baseline characteristics on SLNB positivity was assessed using Cox proportional hazards analysis. Results: 3,600 SLNB performed from 1996 to 2012 of which 969 SLNB (969 pts) reviewed as a pilot. Primary tumor characteristics and demographic details obtained. SLN metastases were detected in 169 pts (17.4%). 134 CLND were performed with 31 pts not having CLND secondary to refusal or early distant metastatic disease. Following CLND, 48 recurrences were observed: recurrence pattern was predominantly cutaneous (19/48 pts, 39.6%), although ipsilateral recurrences in the prior CLND bed were noted (14/48 pts, 29.2%). Visceral recurrences comprised the remainder [non-pulmonary 7/48 pts (14.6%), pulmonary 5/48 pts (10.4%) and CNS 2/48 pts (4.2%)]. Most CLNDs followed by ipsilateral regional nodal recurrences were performed outside tertiary care centers. PFS and OS were significantly worse with increasing stage and SLNB status. Conclusions: AJCC, ASCO and SSO guidelines recommend SLN biopsy for intermediate-thickness melanomas (1-4mm Breslow) to optimize staging accuracy. Incidence of regional recurrence after CLND has been estimated at 30-35%. In this large and uniformly treated series of patients at a major melanoma referral center, SLN were involved in 17.2% and median PFS after CLND was 22mos. Biomarkers associated with SLNB and CLND positivity are currently being evaluated in prospectively banked specimens from patients (07-133) and under the aegis of the SPORE in Skin Cancer (P50CA121973).