OBJECTIVE To document the spectrum of misleading thin-section computed tomographic (CT) diagnoses in patients with biopsy-proved idiopathic pulmonary fibrosis (IPF). METHODS This study had institutional review board approval, and patient consent was not required. Three observers, blinded to any clinical information and the purpose of the study, recorded thin-section CT differential diagnoses and assigned a percentage likelihood to each for a group of 123 patients (79 men, 44 women; age range, 27-82 years) with various chronic interstitial lung diseases, including a core group of 55 biopsy-proved cases of IPF. Patients with IPF in the core group, in whom IPF was diagnosed as low-grade probability (<30%) by at least two observers, were considered to have atypical IPF cases, and the alternative diagnoses were analyzed further. RESULTS Thirty-four (62%) of 55 biopsy-proved IPF cases were regarded as alternative diagnoses. In these atypical IPF cases, the first-choice diagnoses, expressed with high degree of probability, were nonspecific interstitial pneumonia (NSIP; 18 [53%] of 34), chronic hypersensitivity pneumonitis (HP; four [12%] of 34), sarcoidosis (three [9%] of 34), and organizing pneumonia (one [3%] of 34); in eight (23%) of 34 cases, no single diagnosis was favored by more than one observer. Frequent differential diagnoses, although not always the first-choice diagnosis, were NSIP (n = 29), chronic HP (n = 23), and sarcoidosis (n = 9). CONCLUSIONS In the correct clinical setting, a diagnosis of IPF is not excluded by thin-section CT appearances more suggestive of NSIP, chronic HP, or sarcoidosis. (c) RSNA, 2010.