The study of cellular and molecular biology in esophageal carcinomas serves the following purposes: (1) to establish the presence or absence of an infectious cofactor such as human papilloma virus; (2) to understand the genetic mechanisms of disease such as genetic mutations, changes in microRNAs, and the roles of cancer stem cells; (3) to provide prognostic information; and (4) to predict response to medical therapies and new modalities of treatment. In recent years, significant genomic information obtained from the whole genomic sequencing of prospectively collected frozen samples of esophageal carcinomas has opened the field for in-depth understanding of the complex molecular pathways underlying this cancer type. Anti-Her 2 therapy was approved internationally as targeted therapy for esophageal adenocarcinoma of the gastroesophageal junction. Assessment of Her 2 expression is currently the most important molecular test to be performed in clinical settings. The study of cellular and molecular biology of esophageal carcinomas depends on the proper collection of formalin-fixed and snap-frozen tissues as well as blood from patients. Tissue microarray and whole-slide scanning technologies allow tissue research in esophageal carcinomas to progress more efficiently. Cancer cell lines and animal models are valuable to study functional aspects of the various cellular and molecular changes in esophageal carcinomas.