The aim of this study was to analyse allelic loss of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) gene and its protein immuno-expression in dysplastic oral lesions and oral squamous cell carcinomas (OSCCs). Samples were collected from 153 patients [20 ranulas used as a control (C); 30 leucoplakias with mild dysplasia (MD); 30 leucoplakias with moderate to severe dysplasia (MSD); 73 oral squamous cell carcinoma (OSCC)]. PTEN protein expression was investigated using immunohistochemistry, and PTEN allelic loss was analysed by fluorescence in-situ hybridisation (FISH). Differences among groups were evaluated using the χ2 test. PTEN expression was higher in MSD (P=0.002) and OSCC (P=0.0259) compared with the C group; additionally, a higher expression was observed in MSD (P=0.0035) and OSCC (P=0.049) than MD. Regarding FISH analysis, a higher hemizygous (single copy) loss was observed in OSCC than in C (P=0.0467) and in OSCC than in MD (P=0.0175), as well as a higher homozygous deletion in OSCC compared with C (P=0.0159) and OSCC than MD (P=0.0145). The results of this work suggest that PTEN allelic loss is an important mechanism in the late stage of the development of oral potentially malignant lesions into oral cancer.