A 6-year-old male veiled chameleon (Chamaeleo calyptratus) was presented for mass removal on the right mandible. Histopathology revealed an iridophoroma, a subclassification of chromatophoromas. Several months later the chameleon was euthanized and the necropsy, combined with histopathology, indicated metastasis of a mixed chromatophoroma within the skin and to the lungs and testicle. The tumor was further subclassified as a mixed iridophoroma and xanthophoroma based on ultrastructure. Other pathologic findings included marked hepatic fibrosis and severe biliary hyperplasia and severe bilateral cystic glomerulopathy. This case demonstrates the malignant potential of chromatophoromas in chameleons and highlights the need for ultrastructural examination of these tumors for proper subclassification.