Neoadjuvant therapy is increasingly used to treat patients with a wide variety of malignancies. Histologic evaluation of treated specimens provides important prognostic information and may guide subsequent chemotherapy. Neoadjuvant therapy is commonly employed in the treatment of locally advanced rectal adenocarcinoma, hepatic colorectal metastases, esophageal/esophagogastric junction carcinoma, and pancreatic ductal adenocarcinoma. Numerous tumor regression schemes have been used in these tumors and standardized approaches to evaluate these specimens are needed. In this review, the various tumor regression scoring systems that have been used in these organs are described and their associations with clinical outcomes are discussed. Recommendations regarding how to handle and report the histologic findings in these resections specimens are provided.