Pyomyositis is an infection of skeletal muscle that involves the formation of intramuscular abscesses. It occurs most commonly in immunocompromised patients. Pyomyositis caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli has never been reported in the literature. A 48-year-old female patient developed ESBL-producing E. coli bacteremia and pyomyositis on the twelfth day of cefpirome therapy for neutropenic fever after chemotherapy due to acute myeloid leukemia. She recovered completely after a three-week course of meropenem and surgical excision. Pyomyositis should be included in the differential diagnosis when fever and muscular swelling develop in a patient with neutropenic status after chemotherapy. Early recognition of symptoms and proper diagnostic procedures are key to diagnosing pyomyositis. Both adequate antibiotics and surgical intervention are important for the successful treatment of pyomyositis caused by ESBL-producing E. coli.