Objectives: Only few studies on gingival lesions considered large enough populations and contemporary literature does not provide a valid report regarding the epidemiology of gingival lesions within the Italian population. The histopathological and clinical appearance of 538 gingival lesions from northern Italians are described and discussed here. Study Design: The case records of patients referred for the diagnosis and management of gingival lesions, from October 1993 to October 2009, were reviewed. Data regarding the histological type of lesion were also obtained from the biopsy register for each case, and blindly re-examined. Results: We reported a greater frequency of benign lesions (reactive and/or inflammatory) in non-plaque/non- calculus induced gingival disorders. We confirmed an unambiguous prevalence of oral squamous cell carcinoma above all other malignant neoplasia, and a prevalence of neoplastic malignant lesions in the maxilla, with a slight increase in females and a drift of the incidence peak from the seventh to the eighth decade. There was a prevalence of precancerous gingival lesions in the maxilla, with a higher incidence in females and with a drift from the sixth to the seventh decade. We also reported a prevalence of oral lichen planus and lichenoid lesions as major manifestations of desquamative gingivitis. Conclusions: The high frequency of gingival involvement of such different diseases emphasizes the importance of histological characterization and differential diagnosis for periodontists, but more prospective studies are needed to better describe the true incidence of the non-plaque related gingival diseases.