Mohs micrographic surgeryMohs micrographic surgery (MMS) is a frozen sectionFrozen sections technique well suited for removal of some of the more difficult cutaneousCutaneous malignancies. The primary emphasis of the procedure is histologic examination of the entirety of surgical margins, which is done intraoperatively prior to wound closure. There are, on occasion, instances where the microscopic interpretationInterpretation during MohsMohs is hindered by dense inflammation or abundant scar tissue, and additional cases where subtle perineural or skeletal muscle invasion may go undetected in frozen sectionsFrozen sections. For melanomaMelanoma patients, the problem is difficulty in locating melanocytes on H & E stained frozen sectionsFrozen sections, especially for tumors that arise on chronically sun-damaged skin. ImmunostainsImmunostain can be extremely helpful for visualizing tumor in frozen sectionsFrozen sections and are being used more frequently by MohsMohs surgeons when H & E alone is deemed insufficient. We intend to review the full spectrum of immunostaining techniques used in MohsMohs, many of which are simply modifications of immunoperoxidaseImmunoperoxidase protocols employed in permanent sections. A perceived drawback is the delay in surgery associated with tissue processing and the technical aspects of immunostaining. The time required to process each MohsMohs layer varies with the antibody, but many of the newer protocols require as little as 20 min to complete. Currently, immunostains are used during MMS for melanomaMelanoma, basal cell carcinomaBasal cell carcinoma, squamous cell carcinomaSquamous cell carcinoma, dermatofibrosarcoma protuberansDermatofibrosarcoma protuberans, extramammary Paget’s diseaseExtramammary Paget’s Disease (EMPD), granular cell tumorGranular cell tumor, primary mucinous carcinomaPrimary mucinous carcinoma, and trichilemmal carcinomaTrichilemmal carcinoma, and these immunostainsImmunostain are summarized in this chapter.