The appendix is a short intestinal protrusion connected to the cecum (a pouch-like structure located at the junction of the small and large intestine), and averages around 9 cm in length. The appendix is connected to the mesentery by a region called the mesoappendix which store fat as well as supply the intestines with blood, lymphatics and nerves.

The inner lining, facing the lumen of the appendix, is covered by a glandular epithelium with intestinal mucus glands that extend into the deeper layers of the mucosa. The glands are lined with epithelial cells (simple columnar epithelium) and a high number of mucin producing goblet cells. Goblet cells are characterized by a large globule of mucus located in the top portion of the cell. The lamina propria typically contains lymphocytes that partly obscure the underlying muscularis mucosae, which separates the mucosa from the submucosa.

The submucosa is almost fully occupied by lymphoid tissue mainly arranged in primary and secondary lymphoid follicles. The lymphoid follicles are recognized by a circular aggregation of densely packed lymphocytes, sometimes surrounded by darkly stained mantle area of lymphocytes. The center of the secondary lymphoid follicles stain lighter and are termed germinal centers. The germinal centers stain darker and contain larger dividing lymphoblasts, similar to the arrangement in lymph nodes. The outer portions of the submucosa harbor larger vessels and have less dense infiltrates of immune cells.

Similar to the colon, an inner circular muscle layer and a thin external longitudinal muscle layer comprise the muscularis externa that encircles the appendix. Outside of the muscular layers there is a serosa containing loose connective tissue, vasculature and nerves. The outermost located peritoneum consists of a thin lining of mesothelial cells.