•A rapid sensitive method to obtain DNA from saliva allowed detection of VZV DNA in 100% of patients with acute herpes zoster before treatment.•Passive drool and synthetic swab yielded abundant amounts of total DNA.•High-speed centrifugation significantly reduced the time to process saliva from collection to obtaining DNA.•VZV DNA was found exclusively in the pelleted fraction of saliva. VZV reactivation produces zoster (shingles) which may be further complicated by meningoencephalitis, myelopathy, vasculopathy and multiple ocular disorders. Importantly, these neurological and ocular complications of VZV reactivation can occur without rash. In such instances, virological verification relies on detection of VZV DNA or anti-VZV IgG antibody in cerebrospinal fluid (CSF), or less often, the presence of VZV DNA in blood mononuclear cells or anti-VZV IgM antibody in serum or CSF. If VZV were readily detected in other tissue samples (e.g., saliva or tears) in patients with neurological disease in the absence of rash and shown to correlate with the standard tests listed above, more invasive tests such as lumbar puncture might be obviated. In patients with acute herpes zoster, the yield of cell DNA was greater in saliva collected by passive drool or synthetic swab than by cotton swab. The time to process saliva from collection to obtaining DNA was 1h. VZV DNA was present exclusively in the pelleted fraction of saliva and was found in 100% of patients before antiviral treatment. This rapid sensitive method can be applied readily to saliva from humans with neurologic and other disease that might be caused by VZV in the absence of rash.