Background: Verrucous hyperplasia is one of the pre-malignant lesions of oral cancer, thus it is worthy of considerable clinical attention. The aim of this study is to discuss the clinical presentation, related factors, pathologic features and therapeutic modalities of oral mucosal verrucous hyperplasia by statistical analysis. Methods: This is a retrospective study of 26 cases with oral mucosal verrucous hyperplasia in their pathologic report from Jan. 2003 to Jan. 2006. We apply statistical analysis of age, gender, history of smoking, drinking and betel nut chewing, lesion site, multi-centricity, and other complicated oral mucosal pathologic changes. Diagnosis, treatment and follow-up are also included. Results: The twenty-six patients included were all males with a mean age of 55 years. Lesion sites originated from 18 buccal areas, 3 hard palates, 3 lower lips, 2 soft palates, 2 gingivals, 1 oral tongue and 1 retromolar trigone area. There were 19 cases without any prior oral mucosa pathologic history. For those with previous oral mucosa pathologic lesions, 6 cases are in the same site of origin with newly diagnostic verrucous hyperplasia, except one case with prior squamous cell carcinoma. There were three cases with different preoperative histopathologic reports from final postoperative pathologic diagnoses. In general, our treatment strategy of laserexcision was used for smaller lesions and wide local excision with local buccinators fat pad flap reconstruction was applied for larger lesions with a high risk of coexisting malignancy. The average postoperative follow-up was 8 months. Among them, 11 cases healed without any new clinically detected lesion but we lost contact with 4 cases. The other 11 cases showed recurrence, but no malignant transformation was noted until now under our regular follow up. Conclusion: Our study reflects the complexity and variability of oral mucosal pathology. In our experience, most verrucous lesions can be excised by laser knife but a few lesions are large enough to undergo wide local excision. To establish a clinical diagnosis, multiple site biopsies are essential for larger lesions to distinguish verrucous carcinoma and squamous cell carcinoma. According to recent follow-up result, it is acceptable without missing or misdiagnosis of any epithelial malignancy, but the prognosis of verrucous hyperplasia still requires a longer regular follow-up.