Thirteen cases of juvenile xanthogranuloma (JXG) and 13 cases of adult-type xanthogranuloma (AXG) were compared at the light and immunohistochemical levels. Histologically, four main cell types (vacuolated, xanthomatized, spindle-shaped, and “oncocytic”) were seen in variable proportions (from monomorphous to mixed variants) with different types of giant cells (nonspecific, foreign body, Touton, and “ground-glass”). Giant cells were more prominent in AXG than in JXG; oncocytic cells (characterized by an eosinophilic, slightly granular cytoplasm similar to thyroid oncocytic cells) and mostly periodic acid-Schiff (PAS) negative giant cells with a ground-glass appearance (6 of 26) were not observed in classic JXG (i.e., occurring in children <2 years old). Immunohistochemically, JXG and AXG gave similar results: most xanthogranuloma cells labeled strongly with KiM1P and vimentin, while HHF35 and HAM56 stained less intensively. Factor-XIIIa (FXIIIa), KP1 (CD68), and HAM56 stained mostly in the periphery of the lesions. Some markers gave variable results: peanut agglutinin (PA), 60%; α-1-antitrypsin, 50%; lysozyme, 25%; LN3 (HLA-DR), <10% of cells positive. Others were negative: S-100, MAC387 (LI antigen), LeuM1 (CD15), desmin, smooth muscle-specific actin, and QBENDIO (CD34). This profile helps to delineate xanthogranuloma from histological stimulants such as dermatofibroma (which is FXIIIa +, LN3 +, KP1 −, and PA −) and multicentric reticulohistiocytosis (which is FXIIIa, KP1 +, PA−,andHHF35−).