Laser use for biopsy of suspicious lesions may simulate cytological atypia at the margin of the incisions, challenging pathological diagnosis. Erbium, chromium: yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser has shown promising results in experimental models by inducing fewer artifacts. The aims of this study were to examine the thermal wounds induced by Er,Cr:YSGG laser in a short series of oral leukoplakias in terms of cytological and epithelial architectural changes and also to assess the width of the thermal damage lateral to the incision. Four oral leukoplakia patients entered the study and underwent complete surgical excision of their lesions by using Er,Cr:YSGG laser. Patients were weekly controlled until complete healing was accomplished. The patients were included on the existing follow-up program for these lesions thereafter. Study samples were routinely processed by the same technician and double-blindedly studied by two pathologists until a consensus was reached for each case. The pathological analysis of the samples revealed no autolysis and no fixation- or handling-related artifacts. However, cellular and nuclear polymorphism could be observed in two samples. Loss of intercellular adherence was the most frequent thermal artifact in this series; all pseudodysplastic artifacts recognized in the study were of low intensity and located at the basal and suprabasal layers of the leukoplakias' epithelium. The width of the thermal damage at the edge of the incision scored an average of 26.60 ± 25.3 μm. It is concluded that irradiation with Er,Cr:YSGG laser induces a minimal amount of thermal artifacts at the surgical margins of oral leukoplakias and avoids diagnostic interferences with real dysplastic borders.