Staging of cancer is a shorthand system of describing the extent of disease. Pathological staging, often called microstaging, uses the methods of histopathology to achieve this goal. Microstaging for melanoma utilizes attributes that are associated with outcome, generally in association with prognostic models that allow for estimation of survival rates, based on large groups of patients with similar tumors. Microstaging can be performed on primary tumors and to a lesser extent on metastases. Attributes that are important in microstaging in primary tumors include, in particular, those that are utilized in the AJCC/UICC staging system. These are, more or less in order of importance, Breslow's thickness, ulceration, and mitogenicity (the presence or absence of mitoses). Other attributes that have relevance to prognosis at least in some well-conducted studies include tumor-infiltrating lymphocytes, lymphovascular invasion, perineural invasion, Clark's level of invasion, the presence or absence of vertical growth phase and of regression, and other attributes. The pathologic interpretation and significance of these “prognostic variables” are discussed in this chapter. In addition, prognostic models including the AJCC staging system are presented in some detail.