In order to better characterize bacteremic cellulitis caused by Streptococcus pneumoniae, a review was conducted of 10 cases of bacteremic pneumococcal cellulitis, which represented 0.9% of all cases of pneumococcal bacteremia (n=1,076) and 3.2% of all cases of community-acquired bacteremic cellulitis (n=312) that occurred in the Hospital de Bellvitge, Barcelona, from 1984 to 2001. In addition to these 10 cases, 28 cases of bacteremic pneumococcal cellulitis from the literature (Medline 1975-2001) were reviewed. Pneumococcal cellulitis of the face, neck, and trunk was observed more frequently in patients with systemic lupus erythematosus and hematologic disorders, while pneumococcal cellulitis of the limbs was more common in patients with diabetes, alcoholism, and parenteral drug use. In the Hospital de Bellvitge group, bacteremic cellulitis due to Streptococcus pneumoniae was more frequently associated with severe underlying diseases than that due to Staphylococcus aureus or Streptococcus pyogenes (100%, 57%, and 72%, respectively;P=0.01). A concomitant extracutaneous focus of infection (e.g., respiratory tract infection) suggesting hematogenous spread with metastatic cellulitis was more frequent in patients with pneumococcal cellulitis, while a local cutaneous entry of microorganisms was feasible in most patients with Staphylococcus aureus or Streptococcus pyogenes cellulitis. The 30-day mortality was 10% in patients with pneumococcal cellulitis, 13% in patients with Staphylococcus aureus cellulitis, and 23% in patients with Streptococcus pyogenes cellulitis (P=0.3). Thus, bacteremic pneumococcal cellulitis is an unusual manifestation of pneumococcal disease and occurs mainly in patients with severe underlying diseases. In most cases, pneumococcal cellulitis has a different pathophysiologic mechanism than cellulitis caused by Staphylococcus aureus or Streptococcus pyogenes.