BACKGROUND Sjögren's syndrome (SS) and sarcoidosis are diseases of unknown origin that are considered to result from abnormal regulation of the immune system. Pulmonary involvement by SS and sarcoidosis may have similar clinical and radiographic manifestations, making it difficult for the clinician to distinguish between these diseases. OBJECTIVE This study was undertaken to analyze the characteristics of SS and sarcoidosis in the lung to identify distinguishing features that may assist clinicians in the differentiation of these conditions. METHODS We present two cases with severe pulmonary impairment in which the distinction between SS and sarcoidosis required lung tissue biopsy. The literature regarding the pulmonary manifestations of these diseases is reviewed. RESULTS The clinical, pathological, radiographic, and physiological characteristics of lung disease in the setting of SS and sarcoidosis can be very similar, preventing a diagnosis solely on clinical grounds. This is exemplified in the two cases reported. In one patient who carried the diagnosis of sarcoidosis, examination of lung tissue revealed lymphocytic interstitial pneumonitis consistent with SS. In the other patient, who had previously been diagnosed with SS on clinical grounds, examination of lung tissue showed lymphocytic interstitial pneumonitis with scattered noncaseating granulomas, suggesting the possibility of coexisting SS and sarcoidosis. A literature review indicated that lung involvement by SS may be difficult to distinguish from that of sarcoidosis. Furthermore, several cases have been reported in which both diseases coexisted. CONCLUSIONS Because SS and sarcoidosis may coexist and present with similar pulmonary manifestations, aggressive evaluation including tissue biopsy may be required. However, even tissue biopsy may not distinguish between these entities unless noncaseating granulomas are seen (in the case of sarcoidosis) or isolated lymphocytic interstitial pneumonitis is detected (in the case of SS). When both features (ie; noncaseating granuloma and lymphocytic interstitial pneumonitis) are encountered in the same organ, we believe these diseases are coexisting. Distinguishing both conditions may have prognostic implications, because sarcoidosis may present as an autolimiting process and frequently resolves spontaneously without significant residual functional impairment. In contrast, pulmonary involvement with SS often leads to permanent defects and may progress to incapacitating disease.