As with timing, the optimal site of sampling varies between different conditions, and is dependent on whether the sample is intended for immunofluorescence or light microscopy. For many active inflammatory conditions, a biopsy sample that includes the advancing edge of the lesion and established abnormal skin will be optimal. This should not be taken to imply that biopsies containing significant amounts of normal perilesional skin are required. Indeed, sampling of clinically normal skin at the expense of lesional tissue is generally unproductive for histological purposes (Figure 1). While there are exceptions to this rule, they are uncommon, comprising subtle disorders where quantitative differences from the adjacent normal skin are diagnostically important (eg circumscribed acral hypokeratosis, atrophoderma of Pasini and Pierini).