We report a case of generalized dermatitis and itch induced by a possible drug-food interaction in a young woman who was consuming clomipramine for Obsessive Compulsive Disorder (OCD). A 33-year-old woman affected by anxiety symptoms presented to our observation for a clinical evaluation. After psychiatric evaluation, the diagnosis of OCD was performed according to DSM-IV-TR and a pharmacological treatment with clomipramine (75-100 mg/day) plus alprazolam (0.5 mg/day) was started. About one month later, the patient developed a severe generalized urticaria with intense itch. A new anamnesis revealed that on the day before the development of the skin rash, no other drug was consumed and the patient had eaten codfish; clomipramine was then gradually discontinued and changed into paroxetine (30 mg/day). At the moment the patient does not show any OCD related symptom and any adverse event to paroxetine treatment has been recorded. We postulate a possible interaction between clomipramine and codfish ingestion. Allergic potential of clomipramine was investigated, while clomipramine de-challenge induced a decrease of the skin rash, the drug re-challenge performed one month later did not induce any adverse event. In contrast, when the combined re-challenge of codfish and clomipramine was performed urticaria was newly observed. The Naranjo Probability Scale Score suggested a probable causal relationship between drug-food interaction and the skin rash. In conclusion, we suggest evaluating also the complete risk of drug-food interaction occurring on clomipramine treatment.