Mycoplasma pneumonia must be differentiated from other causes of pneumonia, chest pain, and cough, such as other infectious causes, aspiration pneumonia, pneumonitis, lung abscess, empyema, COPD exacerbation, asthma, interstitial lung disease, cardiac diseases, and malignancies.

Differential diagnosis for Mycoplasma pneumonia includes the following:

• Other causes of bacterial pneumonia
• Viral pneumonia
• Fungal pneumonia
• Pneumocystis pneumonia
• Aspiration pneumonia
• Tuberculosis
• Chlamydia infection (including C. trachomatis, C. psittaci, and C. pneumoniae)
• Empyema
• Lung abscess
• Bronchiectasis
• COPD exacerbation
• Asthma
• Interstitial lung disease
• Lung tumor
• Pulmonary embolism
• Pneumothorax
• Hemothorax
• Epiglottitis
• Croup
• Respiratory distress syndrome
• Atelectasis
• Congestive heart failure
• Myocardial infarction
• Pericarditis
• Endocarditis
• Myocarditis
• Cardiomyopathy
• Lymphoma
• Leukemia
• Sarcoidosis

Mycoplasma pneumonia must be differentiated from other diseases that cause atypical pneumonia such as Q fever and legionella

Disease	Prominent clinical features	Lab findings	Chest X-ray
Q fever	Q fever is characterized by abrupt onset of fever, myalgia, headache, and other constitutional symptoms. Cough is the most prominent respiratory symptom and it is usually dry.[1] Cough is associated with dyspnea and pleuritic chest pain.	Antibody detection using indirect immunofluorescence (IIF) is the preferred method for diagnosis. PCR can be used if IIF is negative, or very early once disease is suspected. C. burnetii does not grow on ordinary blood cultures, but can be cultivated on special media such as embryonated eggs or cell culture. A two-to-three fold increase in AST and ALT is seen in most patients.
Mycoplasma pneumonia	Mycoplasma pneumonia can be asymptomatic. Headache, nausea, and malaise usually precede the onset of symptoms.[1] Cough is intractable and nonproductive.	Postitve Coombs test Leukocytosis Thrombocytosis
Legionellosis	Legionellosis is characterized by cough that is slightly productive.[1] Constitutional symptoms such as chills, myalgia, and arthralgia. Gastrointestinal symptoms such as diarrhea, nausea, and vomiting.	Labs are nonspecific for diagnosing legionellosis Renal and hepatic dysfunction Thrombocytopenia and leukocytosis Hyponatremia
Chlamydia pneumonia	There are no specific clinical features of chlamydia pneumonia. Symptoms appear gradually. Chlamydia infection is usually associated with upper respiratory tract symptoms (pharyngitis, sinusitis, etc). It might be associated with extrapulmonary maifestations such as meningitis and Guillain-Barre syndrome.[1]	Chlamydia pneumonia is usually associated with normal WBC count. Diagnosed with the presence of antichlamydial antibody (through complement fixation or direct immunofluoroscence) or direct antigen detection.