Ehlers-Danlos syndrome (EDS) is a major inherited connective tissue disorder leading to an impaired extracellular matrix structure. Although several odontostomatologic signs have been reported, their diagnostic accuracy remains to be ascertained. We tested the hypothesis that EDS is associated with an abnormal reflectance of the oral mucosa. Twelve patients with EDS-II or EDS-III and 12 age- and gender-matched controls were examined. Reflectance of the lower gingival and vestibular oral mucosa in the optical spectrum was measured using an imaging spectrophotometer. EDS patients showed significantly higher reflectance values in the 400-590 nm wavelengths (P<or=.0002) and significantly lower reflectance values in the red wavelengths (610-700 nm range, P<or=.025) than did controls. A reflectance cutoff value of >10.51% at the 400 nm wavelength identified the EDS patients with 100% sensitivity and 100% specificity. These findings indicate that an abnormal oral mucosal reflectance is a previously unrecognized clinical marker of EDS.