Background: Reliable evidence to guide the management of melanoma in situ (MIS) and minimize the risk of recurrence is lacking. Objective: To identify clinicopathological predictors of local recurrence (LR) in patients with MIS and evaluate long-term outcomes according to pathological excision margins. Methods: A case-control study of patients with MIS treated at a large Australian melanoma treatment center from January 2008 to December 2012 was undertaken. Clinicopathological characteristics of patients who developed LR and those who did not were compared. Results: LR developed in 34 of 1407 patients with MIS (2.5%). Median time to LR was 20 months. The primary lesion was removed with pathological margins 60y, P