This problem-based guide illustrates key reasoning processes that physicians use to resolve individual clinical problems through the use of electron microscopy. Its format will facilitate learning the case approach for diagnostic ultrastructural pathology using clinical-ultrastructural-pathogenic correlation. A total of 51 cases and a procedural guide for the ultrastructural pathology laboratory are included. The cases were selected according to one of the following four principles: 1) classic cases that were diagnosed readily by light microscopy to facilitate the electron microscopic diagnosis of less classic cases; 2) diagnostic cases, those cases for which ultrastructural analysis was essential for the diagnosis; 3) supportive cases, which are those cases where either the light or the electron microscopic diagnosis is supportive and confirmatory to the other; and 4) new facts cases, which are those that establish new knowledge regarding the pathogenesis of disease using electron microscopy as the investigative modality. The 51 cases are grouped anatomically in eight major categories. Separate indices for presenting symptoms, differential diagnostic groups, ultrastructural pathology criteria, and final diagnostic categories are provided, as well. This guide will be useful to physicians and students of medicine, structure, and disease. It also makes an ideal operational guide and text for support staff training.