BACKGROUND: Mohs micrographic surgery (MMS) continues to become a more common and accepted treatment for lentigo maligna (LM) and lentigo maligna melanoma (LMM). The primary difficulty encountered lies in the accurate identification of atypical single melanocytes to determine tumor-free margins. Numerous methods have been used to better visualize single melanocytes, with varying results. We present our experience using Mel-5 immunostaining in MMS of LM and LMM. METHODS: Two hundred patients with primary or recurrent LM or LMM were treated using MMS from 1999 to 2003 at the University of Minnesota. The initial clinical margins were determined by Wood's light examination, and an initial debulk specimen was taken and sent for formalin fixation and later reviewed by a dermatopathologist. The first Mohs layer was then taken, and staining with hemotoxylin and eosin as well as Mel-5 immunostaining was performed. All patients were followed up to evaluate for recurrence, with a mean follow-up time of 38.4 months. RESULTS: Of the 200 patients treated, only one recurrence was noted. This patient had been treated with excision followed by radiation before MMS. Use of Mel-5 immunostaining added approximately 40 minutes to each stage. Use of the Autostainer Immunostaining System (DAKO, Carpenterina, CA, USA) shortened the added time to 20 minutes. CONCLUSIONS: MMS with Mel-5 immunostaining yielded excellent results in the treatment of LM and LMM, with only one recurrence noted in 200 patients. When an automated immunostainer was used, minimal time was added to each Mohs stage.