Toe-clipping is a commonly used method to mark reptiles and amphibians, collect genetic information, and collect samples to identify disease. Institutional animal care and use committees impose restrictions on such practices in an effort to mitigate pain inflicted on research animals. However, what is considered “painful” is often based on anthropomorphic intuition rather than scientific evidence. While there is no way to quantify pain, plasma corticosterone levels can provide a measure of the stress caused by procedures. Such data can provide animal care and use committees with the quantitative data they need to make appropriate decisions regarding procedures. We measured and compared plasma corticosterone levels in control, handled, and toe-clipped Cane Toads (Rhinella marina) to determine the extent to which toe-clipping induces stress. While both handling and toe-clipping did significantly increase corticosterone levels when compared with toads that had not been handled, we found no difference in corticosterone levels between Cane Toads that were handled only and Cane Toads that had been handled and had their toes clipped. We therefore conclude that toe-clipping does not cause a greater stress response than does handling.