Tissue-based cyclic immunofluorescence (t-CyCIF) is optimized for FFPE specimens mounted on glass slides. Dewaxing and antigen retrieval are important steps to remove wax and expose antigenic sites. This protocol describes dewaxing and antigen retrieval on a Leica Bond RX automated slide processor; similar instruments are manufactured by Ventana or Dako and are commonly found in histopathology core facilities. t-CyCIF can also be performed following manual de-waxing and antigen retrieval (e.g. microwaving slides in citrate buffer or using a pressure cooker).