In recent years, viridans streptococci have been reported with increasing frequency to cause infections in neutropenic cancer patients. Streptococcus mitis, one of the species included among viridans streptococci, is the most resistant to beta-lactam antibiotics in this group. Bacterial meningitis presenting without pleocytosis in the cerebrospinal fluid (CSF) is rare, and this situation could be confusing to physicians. It is also an uncommon infectious complication in leukemic patients with neutropenia. In patients with leukopenia caused by myelosuppression after chemotherapy, bacterial meningitis must be considered a possibility when a patient develops meningeal signs, even if no pleocytosis is found in the CSF. We report on a 6-year-old boy with leukemia and neutropenia who developed sepsis and meningitis caused by S. mitis with high-level resistance to penicillin and cephalosporins (MIC of both, >2 mg/l); he was a long-term survivor receiving chronic trimethoprim-sulfamethoxazole prophylaxis. The patient was successfully treated with a combination of vancomycin, ceftriaxone, and granulocyte-colony-stimulating factor.