The goals of this document are to provide guidance on the collection of morphologic data and preparation of thyroid tissues, from Xenopus laevis, for histopathological analysis to fulfill the needs of the Amphibian Metamorphosis Assay. This document draws from the guidance developed for the “Histopathology guidelines for Phase 1B of the OECD Fish Screening Assay for EDC’s” and the guidance given in the general protocol for the Phase 2 Amphibian Metamorphosis Assay. The recommended procedures were derived from pathologists experienced with preparing and analyzing thyroid tissues of Xenopus laevis, from previous documents relating to histotechniques associated with preparing amphibian tissues, and from the scientific literature. The procedures are to guide the handling of animals and preparation of tissues for thyroid histology. These methods may not apply to studies that involve other amphibian species, at earlier or later life stages, under alternate treatment durations, or for different desired endpoints.