The clue to skin-cancer behavior is not found in their surface appearance to the naked eye, but in their appearance under the microscope. The nucleus of a cell is the genetic warehouse of information that guides how a cell grows and functions. Usually, cells have only one nucleus or a nucleus of a certain average size. In the case of squamous-cell cancers and melanoma, giant irregular cells packed or crammed with odd-looking nuclear (DNA, genetic) material in the nucleus, usually portend a "bad" histology (appearance under the microscope) and a dangerous prognosis (outcome) for the patient. Cells are usually graded on how they look when compared to the parent cell or a cell of origin. For example, the more bizarre a squamous-cell cancer looks when compared to the normal keratinocytes (parent cells) found in the epidermis, the more atypical (undifferentiated) the skin cancer will appear to the pathologist and the worse the chance for patient survival. Again, the less a squamous cell looks like the parent or normal keratinocyte, the poorer the prognosis (outcome) for the patient.

Basal cells and cancers that have normal-looking nuclei, no matter how badly they behave, may have rooting phenomena and infiltrating patterns of groups of cells that help to determine how the tumor will behave if treated or left untreated.

In summary, the key to predicting tumor behavior is the pathology (different appearance) under the microscope. The interpreted result depends upon the skill of the person reading the specimen. The author usually recommends that skin slides be read only by Board Certified Dermatopathologists, who are trained for years over and above the training of dermatologists and pathologists in the reading of histology (microscopic) slides for skin lesions. They take not only the Board examination for dermatology but a special board exam for dermatopathology as well. The extra training involves study under prominent dermatopathologists for years and, again, taking of a Board examination for this special study. Certified Mohs Surgeons of the American COLLEGE of Mohs Surgery have been shown in numerous blind studies to have a 99.9% agreement with Board Certified Dermatopathologists in analyzing skin cancers. Remember, that similarity of opinion is for skin cancers and does not include skin rashes or eruptions.