An adult male crocodile lizard, Shinisaurus crocodilurus, presented lethargic and cachexic and died three days later. Gross necropsy revealed a darkly pigmented liver and spleen. Histopathologic examination revealed severe, disseminated melanomacrophage hyperplasia confirmed by special staining and electron microscopy. The definitive etiology is unclear, but the time of year and the lizard's age and nutritional state are predisposing factors. The degree o f hepatic melanomacrophage hyperplasia is believed to have impaired liver function and is suspected to have been a significant contributor to the morbidity and mortality in this case. The incidence and roles of melanomacrophages in ectotherms are reviewed.