A practical, transferable microcomputer system for differential diagnosis in dermatopathology, called TEGUMENT, has been developed for use by dermatologists on the standard IBM PC, Compaq, and other compatible personal microcomputers. In an interactive computer program a set of information is abstracted from the microscopic study of each specimen by a dermatologist, to compare with a structured knowledge base. The process leads through a relevant sequence of descriptive phrases until the findings can be allocated to a disease class. The microscopic description and diagnosis are then combined with clinical information by the computer and printed, optionally, as a pathology report. The identification and diagnosis of each case are preserved in permanent memory to enable future search and sorting. The results of independent validation are that a pathologist made the same diagnosis as the machine or a similar differential diagnosis in 91.8%, disagreed in 4.8%, and was unable to make a diagnosis from the description furnished by the machine in 3.4% of 147 actual cases. We conclude that a certain critical minimum of information is required for objective diagnosis; more information is needed for definitive than for differential diagnosis; a characteristic feature is necessary to distinguish between differential diagnoses; an objective description may admit of more than one diagnosis; ambiguity may be reduced by presenting for consideration all distinguishing features that characterize closely related diagnoses; and the personal microcomputer, programmed in this way, is of considerable assistance to the dermatologist in the histopathologic diagnosis of diseases and neoplasms of the skin.