Recognition of the different types of multinucleated giant cells in neoplastic and pseudotumoral lesions of the skin may be helpful in the differential diagnosis of these tumors. In this review, we will analyze the different types of multinucleated giant cells that can be found in nonepithelial cutaneous tumors and, more importantly, the clinicopathological context in which they are found. Touton giant cells are typically present in juvenile xanthogranuloma, necrobiotic xanthogranuloma, and some subtypes of xanthomas. Giant cells with a ground glass appearance are typically present in the solitary reticulohistiocytoma and multicentric reticulohistiocytosis. Osteoclast-like cells are found in giant cell tumors (GCT) of soft parts, plexiform fibrohistiocytic tumor, and atypical fibroxanthoma. Floret-like cells are present in giant cell fibroblastoma, pleomorphic lipoma, multinucleate cell angiohistiocytoma, and giant cell collagenoma.