Five cases of xanthomatosis in geckos were evaluated, one in a northern green gecko (Naultinus grayi) and the remaining four in three species of leaf-tailed geckos (two Uroplatus henkeli, one U. sikorae, one U. fimbriatus). All geckos were females 3-11 yr of age, were clinically ill on presentation, and either died or were euthanized. Necropsies showed emaciation in three geckos, with white nodular foci on coelomic surfaces in two of these geckos. The other two geckos had no gross abnormalities. Histopathologic examination revealed xanthomatosis involving the coelomic surfaces of four geckos and the ventricles of the brain in all geckos. Xanthomas in the brain were associated with various degrees of hydrocephalus. The lesions were comprised of stacks of clear clefts consistent with cholesterol crystals, and these structures were surrounded by epithelioid macrophages, multinucleated giant cells, and lymphocytes. Four geckos had active folliculogenesis, and two had foci of follicular degeneration and localized yolk coelomitis. In all cases, xanthomatosis was believed to have contributed significantly to morbidity and mortality.