Dermatopathology is one of the most powerful diagnostic tools in clinical dermatology. In this diagnostic process, the dermatologist and the dermatopathologist are a team in patient care, where the dermatologist must know when biopsies are indicated; be able to select lesions to biopsy those that are likely to yield diagnostic results; skillfully procure the biopsy samples; and provide the dermatopathologist with an accurate history, clinical description, and clinical differential diagnosis. On the other side, the dermatopathologist should be readily accessible to the clinician, and be dogged in the pursuit of an accurate histological description and clinically relevant diagnosis. In this article, we will discuss the finer points of skin biopsy, benefits and limitations of biopsy interpretation, and the future potential of skin biopsy in the selection of targeted therapy and individualized patient care.