The association of chronic urticaria (CU) to parasitic infestations has been poorly studied. Recently, sensitization to the parasite larva Anisakis simplex has been described as the cause of acute urticaria and anaphylaxis. The aim of this work was to study the relationship between sensitization to A. simplex and CU. One hundred one patients with CU were studied. Data of possible contacts with A. simplex were collected and the usual CU study was performed. Furthermore, total and specific immunoglobulin E (IgE; Pharmacia CAP system IGE fluorescence enzyme immunoassay: CAP) to A. simplex, Ascaris lumbricoides, Echinococcus granulosus, and Toxocara canis were determined as well as skin-prick test with A. simplex and serology to E. granulosus. In accordance with the results of the CAP to A. simplex, the patients were divided into two groups, positive and negative, and, subsequently, subdivided into two other subgroups that were alternatively told to stop eating fish or seafood in their diet or to continue with their normal diet. Checkups were performed at 6, 12, and 18 months. Thirty-five percent of the patients had positive skin tests to A. simplex, and CAP to A. simplex was positive in 55%. The fish-eating habits, acute or chronic gastrointestinal disease, and the background of abdominal surgery were not related to the results of the CAP and/or skin test to A. simplex. A total of 21.8% of all the patients had detectable CAP to A. lumbricoides, 91% of whom had positive CAP to A. simplex. Three patients had specific IgE to T. canis and five patients had specific IgE to E. granulosus, in the absence of positive serology. All had specific IgE to A. simplex. Present infestation could not be proved in any of them. The clinical evolution and variations of CAP to A. simplex and of total IgE were not statistically different among the groups during the 6, 12, and 18 months of the study. The percentage of sensitization to A. simplex in patients with CU is elevated and determines the sensitization to other parasites because of cross-reactivity. We have not found any causal relationship between the presence of specific IgE to A. simplex and CU. The clinical importance of this finding in this disease is still undetermined.