A 42-year-old female, treated with isoniazid, rifampicin, pyrazinamide and ethambutol for multifocal tuberculosis, developed, forty days later, hyperthermia, facial edema, cervical lymphadenopathy and generalized exanthema. Biological test results revealed eosinophilia, atypical lymphocytes, thrombocytopenia and liver injury. DRESS was suspected, and four antituberculosis drugs (ATD) were withdrawn. As patch tests for the four ATD showed negative results, we decided to reintroduce pyrazinamide, ethambutol and rifampicin separately with a three-day interval. Pyrazinamide and rifampicin were tolerated by the patient. However, six hours after receiving ethambutol, she developed fever and generalized rash, with no biological abnormalities, which resolved two days later. Since ethambutol was claimed to be the culprit drug, isoniazid was added, and 10 hours later, the patient developed fever, facial edema, generalized rash, eosinophilia and liver injury. This clinical and biological pattern resolved two weeks later. This report suggests a hypersensitivity relapse to ethambutol after isoniazid-induced DRESS in patients treated with first-line ATD.