Skin biopsy is a common dermatologic procedure that is typically required to assess cutaneous neoplasms and to evaluate indistinct skin eruptions for which a clinical differential diagnosis is considered. Although plenty of literature exists on the histopathologic features of different skin diseases, clues and methods that help maximize the diagnostic results and avoid common pitfalls in the processing of skin biopsies have received little attention. In cutaneous biopsy, interpretation is very important, as is the process of choosing the appropriate biopsy technique. As soon as the decision to perform a skin biopsy is taken and until microscopic slide evaluation occurs, multiple opportunities for error may arise, any of which may disadvantage the pathologist in efforts to reach a definitive diagnosis. Therefore, it is exceptionally important that clinicians work closely with pathologists to optimize biopsy results. The purpose of this review is to increase awareness of the potential for error in the course of obtaining and interpreting biopsy specimens. The process consists of several steps that refer to, respectively: choice of biopsy site; choice of technique; tissue fixation; tissue processing; the pathologist's interpretation; and clinicopathologic correlation. Avoiding these pitfalls may, in turn, maximize the pathologist's ability to make the correct diagnosis and thus provide better patient care.