An accurate assessment of subcutaneous lesions can be made by joining the differential diagnoses generated by clinical and histologic features. Anatomic location of lesions, presence or absence of ulceration, occurrence of lipoatrophy, history of trauma, association with immunologic or metabolic disorders, and age of the patient are important clinical data to consider in conjunction with the microscopic features. Individual histologic features such as calcification, cytophagic histiocytes, pseudocysts, lymphoid nodules, and crystals should be evaluated in conjunction with the inflammatory infiltrate (i.e., granulomatous, neutrophilic, lymphocytic, or combined); presence and type of necrosis (e.g., basophilic, hyaline, lobular, or septal); and presence and extent of sclerosis. For optimal management of patients, it is important to consider the differential diagnosis generated by the dominant histologic features as well as the clinical and histologic abnormalities.