Listeriosis is associated with more than one clinical syndrome. It must be differentiated from other infections that cause fever and systemic/localized symptoms (either CNS disease, gastroenteritis, genitourinary disease, endocarditis, or bacteremia), such as E. coli, Neisseria spp., Streptococcus spp., Staphylococcus spp., Shigella, Salmonella, Campylobacter, Serratia spp., or Haemophilus spp., mononucleosis, or tuberculosis. Listeria monocytogenes must also be differentiated from other organisms that are morphologically similar, such as pneumococci, diphtheroids, or Haemophilus spp. Differential diagnosis of listeriosis additionally includes hematologic malignancies (such as leukemia or lymphoma), thyroid disease, drug fever, vasculitides, or rheumatologic diseases.

The differential diagnosis of listeriosis includes the following:

• Infectious causes of gastroenteritis, such as E. coli, Shigella, Salmonella, or Campylobacter
• Infectious causes of neonatal meningitis, such as E. coli or Group B Streptococcus
• Infectious causes of CNS disease, such as N. meningitidis, Streptococcus spp., or abscess formation
• Infectious causes of genitourinary diseases, such as Candida infections, E. coli, Staphylococcus spp., enterobacteriaceae, Serratia spp., or Hemophilus spp.
• Infectious causes of endocarditis, such as Staphylococcus or enterobacteriaceae
• Other organisms that have morphological resemblance to Listeria, such as pneumococci, diphtheroids, or Haemophilus spp.
• Hematological malignancies
• Tuberculosis
• Infectious mononucleosis
• Sarcoidosis
• Drug fever
• Thyroid disease
• Rheumatologic disease
• Vasculitis