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Due to the great variety of drug-induced adverse side-effects, the causative agent could not be easily determined. Improvement of the clinical picture after cessation of the causative agent, the clinical observations, as well as data given in medical literature might provide useful information for the imputability of a drug. The diagnosis of drug hypersensitivity is difficult, and must be carefully considered. It is needed in cases when the causative agent cannot be replaced by another in the same pharmacological family of the drug and when the patient is in absolute need of the medicine. The aim of this article is to emphasize the required possibilities and arising dangers in the check-up of the patient. In the investigation process at the hospital: a patch test was applied with the possible causative agents: lamotrigine, risperidone, sertraline, zopiclone, atorvastatin. It was sertraline that proved to be positive. Histologic examination taken from the site of positive drug-patch test referred to the original form of the drug-induced adverse side-effect (erythema exsudativum multiforme). Because of the bipolar affective disorder of the patient we executed oral rechallenge of the patient with the cutaneous negative culprit drugs. Oral rechallenge, in spite of being hazardous for the patient, is the only reliable method for detecting the causative agent. However, by the rechallenge with the drugs, even a partial dose of lamotrigine proved to be positive, after 3 hours erythema occurred, and 12 hours later scarlatiniform exanthema developed in spite of intravenous administration of steroid and antihistamine medication. The case's curiosity is that one causative agent proved to be positive by epicutaneous patch test meanwhile another drug was positive by the oral rechallenge. Finally, in spite of being consistent with the clinical picture, only one certain method cannot be totally sufficient and reliable in the investigation process of eliciting the causative agent in patients with adverse drug reactions.