Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous adverse reaction mainly attributed to antibiotics. It is characterized by numerous, nonfollicular, sterile pustules, arising on an exanthematous and edematous base. It is a serious adverse reaction accompanied by fever and leukocytosis. Piperacillin/tazobactam is indicated for the treatment of patients with moderate to severe infections. Herein is reported a case of AGEP caused by piperacillin/tazobactam. A 78-year-old woman with metastatic breast cancer was presented to the emergency department reporting fever and groin pain. The laboratory analysis and more specifically urine cultivation showed a urinary tract infection by E. coli with sensitivity to piperacillin/tazobactam. She had no known allergies. She was started on intravenous piperacillin/tazobactam; she improved clinically on the second day, but on the fourth day of intravenous therapy, she developed extensive pustular rash on the folds and anterior proximal thighs, accompanied by fever and neutrophilia. Piperacillin/tazobactam administration was interrupted and she was given prednisolone for ten days. The patient improved clinically and her laboratory tests returned to normal after two weeks. AGEP is an uncommon side effect of piperacillin/tazobactam treatment and there are few cases reported.