OBJECTIVES: To evaluate a tissue autofluorescence (AF) system as an aid for Dental Hygienist (DH) to screening oral mucosa alterations during supportive periodontal care (SPC). MATERIALS AND METHODS: Two hundred patients in regular SPC with no previous oral mucosa lesions were enrolled. The oral cavity of each patient was examined by a DH without and with the AF system. Afterward, the patient was examined by a General Dentist (GD) by means of conventional visual inspection alone. The primary outcome was the sensitivity of AF system used by a DH. Furthermore, the specificity, predictive values and likelihood ratios were also evaluated. Receiver operating characteristic (ROC) curves were generated and area under ROC (AUROC) was estimated to overall evaluate the ability of DH to detect oral mucosa lesions with and without an AF system. RESULTS: After completion of intraoral screening, 111 and 66 oral mucosa alterations were detected by DH without and with the AF system. A total of 83 lesions were instead recorded by GD with conventional inspection. The sensitivity and specificity of AF system used by a DH were 61.5% and 90.6% while the conventional visual inspection showed a sensitivity of 81.3% and specificity of 97.6%. AUROC values of 0.760 and 0.894 were found for AF system and for conventional visual inspection respectively. CONCLUSIONS: Whitin the limitations of present study, the results showed for DH an increase of specificity and a loss of sensitivity in detection of oral mucosa alterations using the AF system. CLINICAL RELEVANCE: The use of AF system may be considered an aid for DH to improve screening of oral mucosal alterations during SPC.