We report the case of a child presenting with an adverse drug reaction highly suggestive of drug-induced enterocolitis syndrome (DIES) to amoxicillin (AMX). A 10-year-old girl developed repetitive vomiting and pallor without cutaneous or respiratory symptoms 2h after AMX intake. DIES is not a well-described entity, and very few data are available in the literature. In the absence of an existing definition, the diagnosis of DIES can only be suspected and is based on its homology with food protein-induced enterocolitis (FPIES). The major criterion is the recurrence of repetitive and often incoercible vomiting occurring within 1–4h of ingestion of the culprit food in the absence of IgE-mediated allergic classic skin and respiratory symptoms. Once the diagnosis of DIES to AMX is suspected, an open challenge with AMX should be undertaken with caution, under medical supervision in a day hospital unit because of the risk of severe recurrence. Once the diagnosis is confirmed, AMX should be contraindicated to avoid severe reactions.