The excellent cure rates associated with Mohs micrographic surgery depend on accurate interpretation of complete and high-quality microscopic frozen sections. Reliable interpretation of microscopic slides is only possible if the surgeon can distinguish tumor cells from surrounding normal tissue. By highlighting tumor cells with a chromogen that is visible on light microscopy, immunostaining allows the Mohs surgeon to distinguish tumor from normal cells in these challenging scenarios. This article focuses on practical aspects involving the most commonly used immunostains in dermatologic surgery, including MART-1 for melanocytic neoplasms, cytokeratin stains for keratinocytic neoplasms, and CD34 stains for dermatofibrosarcoma protuberans.