Out of 134, 12 sarcoidosis patients with symptoms of mucosal dryness as the first clinical manifestation were identified and compared with 30 consecutive unselected Sjögren's syndrome (SS) patients. Sicca manifestations were similar among the two groups, while parotid gland enlargement (PGE) was more frequently found in sarcoidosis patients (P < 0.05). Patients with sarcoidosis had mainly pulmonary (P < 0.001) and skin involvement (P < 0.05), while SS patients presented more frequently with Raynaud's phenomenon (P < 0.05). Autoantibody profile was more often found in SS patients compared to sarcoidosis (P < 0.0025). The histopathological findings of minor salivary gland biopsy (MSGB) revealed noncaseating granulomas (NCG) in 58% of patients with sarcoidosis, while in SS, MSGB showed focal sialadenitis in the majority of the patients. Transbronchial lung biopsy (TBLB), which was performed in 10 sarcoidosis patients, revealed the presence of NCG in all patients. In patients with sarcoidosis and sicca symptoms as the presenting syndrome, PGE is a useful clinical finding. Searching for pulmonary involvement is a determining factor to differentiate sarcoidosis from SS. The absence of autoantibodies is another useful tool for the diagnosis of sarcoidosis. Finally, MSGB is very helpful to discriminate between sarcoidosis and SS and when MSGB is not specific, then TBLB is valuable to confirm the diagnosis.