Background The diseases that affect the oral cavity are wide and diverse, comprising a broad spectrum of either benign or malignant lesions. However, few histological-based studies were performed for the evaluation of oral cavity lesions, and very few directed to oral soft tissue pathology. The aim of this study was to carry out pioneering research, within a Portuguese population, to determine the frequency and characteristics of oral malignancies, potential malignant disorders, and soft benign tissues pathologies submitted for biopsy in a north Portugal (Oporto) hospital population. Material and Methods We performed a retrospective study of soft tissue, oral cavity biopsies, in a hospital north of Portugal (Oporto) between 1999 and 2006. We analysed information on gender, age, location of the lesion, and the histopathological diagnosis. Results A total of 1042 oral biopsies were observed, 557(53.5%) in females and 485 (46.5%) in males, with a mean age of 51.7 years (S.D. ±17.6). The topographic location most frequently affected was labial mucosa (n=306). Considering the nature of the lesions, 700 (67.2%) corresponded to non-neoplasic lesions, 45 (4.3%) to potentially malignant disorders, and 297 (28.5%) to neoplasms (93 benign and 204 malignant). Non-neoplasic lesions were more prevalent in female gender (59.9%) when compared with potentially malignant disorders (46.7%) and neoplasms (39.4%) (P< 0.001). Non-neoplasic lesions presented the lower mean age (49.2±17.6) and potentially malignant disorders the highest mean age (60.5±14.5) (P< 0.001). The most common lesion of entire sample was fibro-epithelial hyperplasia (n=186; 17.9%), followed by squamous cell carcinoma (n=158; 15.1%). Conclusions Fibro-epithelial hyperplasia, followed by squamous cell carcinoma, was the most common pathologies. This pioneering study provided, for the first time, data about the proportion of squamous cell carcinoma when compared with benign conditions in a Portuguese hospital population. Key words:Oral biopsies, oral cavity, oral pathology, Portugal, soft tissue lesions.