Although tomatoes are a commonly consumed food, severe allergic reactions to tomatoes are unusual or rarely reported. Previously reported allergic manifestations to tomato include urticaria/angioedema, dermatitis, oral allergy syndrome, rhinitis, and abdominal pain. The aim of this study was to report two patients with significant immediate hypersensitivity reactions to tomato and characterize the responsible allergen. We reviewed the history and documentation of tomato-specific immunoglobulin E (IgE) of two patients with adverse symptoms after ingesting tomato. Fresh tomato extracts prepared from the skin, seeds, and flesh of red, ripe tomatoes were evaluated for total protein content and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was performed to characterize the tomato protein. IgE enzyme-linked immunosorbent assay (ELISA) using the patients' serum against the various tomato extracts was accomplished and IgE immunoblot was performed. Percutaneous skin tests or radioallergosorbent tests (RASTs) were positive to tomato in both patients. Both adults experienced laryngeal edema and one had anaphylaxis. Similar total protein contents were found in each of the tomato extracts and gel electrophoresis revealed similar protein profile for skin and seed extracts with protein bands discernible at molecular weights of 21, 33, and 43 kDa. One patient reacted specifically to a 43-kDa protein band on IgE immunoblot. The two cases show that severe allergic reactions to tomato occur in adults and one is associated with IgE binding to a 43-kDa protein.