In the histology laboratory, there is a delicate balance between over-processing or under-processing tissue samples. Formulating the best processing schedule for a histology laboratory becomes daunting when all the influencing factors are considered, such as tissue size, type, volume, and thickness versus time. Many laboratories rely on technical support from equipment representatives to assist in optimizing tissue processing when new processors are being validated. Most processor manufacturers will have suggested processing schedules tested and validated for biopsies and routine surgicals. Because each laboratory differs, the processing programs should be customized to suit the various tissue sizes/types and staining methods. Choosing the proper processing protocol initially will minimize the need for reprocessing and troubleshooting later. On a related note, changes to established processing protocols will require re-validation of subsequent staining processes, including Immunohistochemistry (IHC) and in-situ hybridization (ISH) staining methods.