Dermatological biopsies can be obtained from many anatomic areas and fulfill a variety of diagnostic roles. Due to this variety, the handling and processing of dermatological specimens pose unique challenges. The small size, disparate shapes, and anatomic variation seen on skin biopsies require specialized techniques to enable sufficient sampling, proper orientation, and accurate diagnoses. This chapter addresses issues related specifically to the processing of small specimens, evaluation for biopsies for alopecia, nail specimens, frozen sections, and specimens requiring direct immunofluorescence.