Both Sjögren's syndrome (SS) and nonSjögren's syndrome (NSS) can present with the sicca symptoms of dry eyes and a dry mouth but they are distinct pathological entities that require diagnostic discrimination. This study included 82 sicca syndrome patients and examined the ability of sialoscintigraphy and antibodies against the autoantigens a-fodrin, Ro and La to discriminate between SS and NSS. A total of 30.8% of SS patients compared with 58.8% of NSS patients were a-fodrin positive. The prevalence of Ro positivity was 69.4% for SS patients compared with 0% for NSS patients. The prevalence of La positivity was 52.4% for SS compared with 0% for NSS patients. Sialoscintigraphy showed that more NSS patients had grade III salivary gland impairment compared with SS patients (64.7% versus 19.4%). These data suggest that using sialoscintigraphy in combination with measuring the levels of serum a-fodrin, Ro and La might be useful for SS and NSS discrimination.