Two patients were found to harbor intermediate-level penicillin-resistant Streptococcus pneumoniae in a pediatric hospital setting. For the first patient, the bacterium was isolated from a tracheal aspirate, and for the second patient, a positive blood culture was found a short time after the index case. Two molecular typing techniques (enterobacterial repetitive intergenic consensus sequence polymerase chain reaction, and repetitive sequence-based polymerase chain reaction) demonstrated homology among these isolates, which suggests person-to-person spread. We propose the need for institution-based infection control precautions that will limit the spread of penicillin-resistant pneumococci.