The neural crest (NC) is a remarkable transient structure in the vertebrate embryo that gives rise to a highly versatile population of pluripotent cells that contribute to the formation of multiple tissues and organs throughout the body. In order to achieve their task, NC‐derived cells have developed specialized mechanisms to promote (1) their transition from an epithelial to a mesenchymal phenotype, (2) their capacity for extensive migration and cell proliferation, and (3) their ability to produce diverse cell types largely depending on the microenvironment encountered during and after their migratory path. Following embryogenesis, these same features of cellular motility, invasion, and proliferation can become a liability by contributing to tumorigenesis and metastasis. Ample evidence has shown that cancer cells have cleverly co‐opted many of the genetic and molecular features used by developing NC cells. This review focuses on tumors that arise from NC‐derived tissues and examines mechanistic themes shared during their oncogenic and metastatic development with embryonic NC cell ontogeny. Developmental Dynamics 244:311–322, 2015. © 2014 Wiley Periodicals, Inc.