BACKGROUND There is a paucity of data or publications in the literature on best practices for opening a new Mohs surgery unit. OBJECTIVE The goal of this article is to be a “how to” guide for starting a Mohs and dermatologic surgery practice. MATERIALS AND METHODS Two academic Mohs surgeons share their personal experiences and data from the literature. RESULTS Topics discussed include picking a location and identifying space, equipment, staffing, regulatory practices, policies and procedures, marketing and outreach, patient experience, building culture, clinic efficiency, and vision. CONCLUSION Although opening a new Mohs surgery unit is challenging, it can be rewarding to have the opportunity to develop best practices and systems that create a wonderful working environment and allow for exceptional care of patients.