Noninfectious or unusual infectious diseases may present with clinical, radiological and laboratorial characteristics of community-acquired pneumonia (CAP). Usually their presence is only suspected after treatment failure, leading to inappropriate interventions, unnecessary costs and risks related to the untreated potentially life-threatening disease. The present study aimed to assess the noninfectious or unusual infectious diseases that may be misdiagnosed as CAP that progresses with treatment failure. Sixteen hospitalized patients with presumptive diagnosis of CAP and treatment failure were described. The most prevalent symptoms were fever and cough. Radiological pattern of air-space disease was observed in 10 (62%) patients. The diagnosis was established by autopsy (12%) or invasive procedures (88%), as follows: open lung biopsy (nine), flexible fiberoptic bronchoscopy (two), transthoracic fine needle aspiration (two) and bone marrow aspiration (one). Eight patients had noninfectious diseases: pulmonary embolism, cryptogenic organizing pneumonia, Wegener's granulomatosis, hypersensitivity pneumonitis, bronchocentric granulomatosis, neoplastic disease and acute leukemia. The unusual infectious diseases were: tuberculosis, cryptococcosis, actinomycosis, histoplasmosis and paracoccidioidomycosis. Patients with noninfectious or unusual infectious diseases may present with symptoms and radiological findings that mimic CAP. These diseases should always be suspected in patients who do not respond to initial empirical antimicrobial treatment, especially young patients or those without comorbidity.