Rothia mucilaginosa is a gram-positive coccus that poses a diagnostic challenge and often requires DNA pyrosequencing for diagnosis as it can be easily mistaken for coagulase-negative staphylococci on initial culture results. While it is often times normal human oral and upper respiratory tract microbiota, it can be a virulent pathogen in immunocompromised patients. Most commonly, it causes bacteremia (catheter and non-catheter related) and meningitis in these patients. Our objective was to report the incidence of R. mucilaginosa infections in neutropenic children with hematological malignancies or following hematopoietic stem cell transplantation at a major children's hospital. We report 11 patients in this cohort who developed clinically significant R. mucilaginosa infections, including three deaths directly attributable to this microorganism. Three patients developed significant neurological involvement, accounting for two of the deaths, and one patient died of disseminated infection. Except for one, all patients had severe neutropenia, central line catheters, and mucosal breakdown at the time of infection. Patients who succumbed never achieved neutrophil recovery. In conclusion, R. mucilaginosa can lead to life-threatening infections in immunocompromised hosts, especially in profoundly neutropenic patients.