Clinicians often receive pathology reports proclaiming a spongiotic dermatitis with little in the form of a cogent differential diagnosis. In some cases, this is a natural consequence of the nonspecific nature of the reaction pattern due to matters of sampling error and/or lesional evolution. Further, some conditions are so synonymous in their histologic presentation that to choose one without mention of the other, purely on a histologic basis, may serve to inadvertently mislead the clinician. Despite the often significant histologic overlap amongst the varying spongiotic dermatitides, there are many subtle, yet detectable, features that may serve as clues to the pathogenetic process. Identification and subsequent communication of these features help to narrow the diagnostic possibilities with the ultimate goal of contributing to effective patient management. This article focuses on the histologic details of the spongiotic reaction pattern and presents some of the more common variations of its manifestation which, in conjunction with ancillary inflammatory elements, may help the histomorphologist to arrive at a more concise list of diagnostic possibilities.