Introduction: Hypersensitivity reactions to macrolides are rarely described in the literature wherefore they are considered one of the safest choices for antibiotic treatment. Out of the reported reactions, cutaneous manifestations have the highest frequency, particularly non-immediate ones. Materials and methods: We report a case of a 71-year-old female who was referred to us for the drug allergy work-up of a rash unaccompanied by systemic signs, compatible with symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) induced by clarithromycin. Results: The diagnosis was confirmed by a drug provocation test, which reproduced the index reaction. Discussion: As SDRIFE is quite infrequent, it can easily be misdiagnosed if the patient cannot present a clear history of the index reaction or the causal connection with the incriminated drug is not clear. Despite the fact that macrolides rarely induce hypersensitivity reactions, they must not be overlooked in the assessment of a drug induced reaction, as they are a potential etiological factor.