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Worldwide, sentinel node biopsy (SNB) is now a standard staging procedure for most patients with melanomas 1 mm or more in thickness, but its therapeutic benefit is not clear, pending randomized trial results. This study sought to assess the therapeutic benefit of SNB in a large, nonrandomized patient cohort.Patients with primary melanomas 1.00 mm or more thick or with adverse prognostic features treated with wide local excision (WLE) at a single institution between 1992 and 2008 were identified. The outcomes for those who underwent WLE plus SNB (n = 2909) were compared with the outcomes for patients in an observation (OBS) group who had WLE only (n = 2931). Median follow-up was 42 months.Melanoma-specific survival (MSS) was not significantly different for patients in the SNB and OBS groups. However, a stratified univariate analysis of MSS for different thickness subgroups indicated a significantly better MSS for SNB patients with T2 and T3 melanomas (>1.0 to 4.0 mm thick) (P = 0.011), but this was not independently significant in multivariate analysis. Compared with OBS patients, SNB patients demonstrated improved disease-free survival (DFS) (P < 0.001) and regional recurrence-free survival (P < 0.001). There was also an improvement in distant metastasis-free survival (DMFS) for SNB patients with T2 and T3 melanomas (P = 0.041).In this study, the outcome for the overall cohort after WLE alone did not differ significantly from the outcome after additional SNB. However, the outcome for the subgroup of patients with melanomas more than 1.0 to 4.0 mm in thickness was improved if they had a SNB, with significantly improved disease-free and DMFS.