Epithelial cancers have served as a paradigm to study tumor dissemination but recent data have highlighted significant differences with nonepithelial cancers. Here, we review the current knowledge on nonepithelial tumor dissemination, drawing examples from the latest developments in melanoma, glioma, and sarcoma research. We underscore the importance of the reactivation of developmental processes during cancer progression and describe the nongenetic mechanisms driving nonepithelial tumor spread. We also outline therapeutic opportunities and ongoing clinical approaches to fight disseminating cancers. Finally, we discuss remaining challenges and emerging questions in the field. Defining the core principles underlying nonepithelial cancer dissemination may uncover actionable vulnerabilities of metastatic tumors and help improve the prognosis of patients with cancer