Mesenchymal neoplasms of the gastrointestinal tract are rare compared with epithelial lesions. However, over the past few decades, the increasing volume of gastrointestinal endoscopy has expedited the recognition of several novel entities with varying clinical significance. Its spectrum extends from reactive changes and benign neoplasms to highly aggressive sarcomas. At the malignant end of the spectrum, the importance of correctly diagnosing these tumors is underscored by the specific therapeutic implications available for some tumor types (eg, tyrosine kinase inhibitors for gastrointestinal stromal tumors) that allow personalized treatments. Benign lesions frequently surface among routine polypectomy specimens, sometimes offering diagnostic challenges. However, precise classification is the only way to avoid prognostic uncertainty and overtreatment, and to recognize possible syndromic associations. Hereby, we offer a pragmatic review of the topic from the gastrointestinal pathologist's perspective, who, although more accustomed to epithelial neoplasms, can use an algorithmic approach to diagnose mesenchymal entities successfully.