Zebrafish has proven to be a highly versatile model for comprehensive studies of gene function in development. Given that the molecular pathways involved in epithelial carcinogenesis appear to be conserved across vertebrates, zebrafish is now considered as a valid model to study tumor biology. Development and homeostasis in multicellular organisms are dependent on a complex interplay between cell proliferation, migration, differentiation, and cell death. The Wnt signaling pathway is a major signaling pathway during embryonic development and is the key regulator of self-renewal homeostasis in several adult tissues. A large body of knowledge on adult stem-cell biology has arisen from the study of the intestinal epithelium over the past 20 years. The Wnt pathway has appeared as its principal regulator of homeostatic self-renewal. Moreover, most cancers of the intestine are caused by activating mutations in the Wnt pathway. Recently, zebrafish models have been developed to study Wnt pathway-induced cancer. An appealing avenue for cancer research in zebrafish is large-scale screens to identify chemotherapeutic and chemopreventive agents in conjunction with the in vivo imaging approaches that zebrafish affords.