Vitamin and mineral supplements are commonly used in diets for zoologic and companion animals. Because specific nutrient requirements are often unknown, informed decisions are based on literature for related species. Over 18 mon beginning in November 2017, an entire population of spot-tailed earless lizards (Holbrookia lacerata and Holbrookia subcaudalis) died (N = 33). All but two lizards were submitted for histopathology (94%). All examined cases had mineralization in at least one tissue; 71% (22 of 31) had multisystemic mineral deposits consistent with metastatic mineralization. No underlying causes were detected histologically. The supplement used for dusting the food items fed five to six times per week was inadvertently switched for 2 to 4 mon, and the incorrect supplement was found to contain fourfold the intended vitamin D3 concentration. Thus, hypervitaminosis D was considered the most likely cause. Interestingly, eastern collared lizards (Crotaphytus collaris), also fed prey supplemented five to six times a week, and over 50 other insectivorous reptile and amphibian species possibly receiving the supplement one to seven times a week did not appear affected. During this time, only two other cases of metastatic mineralization were diagnosed in other herpetofauna at this institution. Prior to receiving the incorrect supplement, there were no cases of metastatic mineralization detected in the earless lizard population. These cases highlight species-specific sensitivities, and the deleterious effects of excessive or inappropriate supplementation. It is important to confirm product identification on arrival, regularly conduct chemical analysis of supplements, and educate keepers and owners about adverse effects of inappropriate supplementation.