Purpose: People with moderate to severe gingival or mucosal pigmentation usually demand treatment for esthetic reasons and/or anxiety about appearance. The present study clinically evaluates the effectiveness of CO₂ laser to eliminate abnormal deposition of melanin in the oral tissues. Materials and Methods: In this study, 28 different melanin pigmented mucosal sites of 17 patients were depigmented with CO₂ laser. Results: The treated areas appeared normal within 2 to 3 weeks after performing one-step laser surgery and in all but one case remained depigmented during the follow-up period of 5 years. Conclusion: The CO₂ laser appears to have a place in the treatment of melanin pigmented tissues and offers a reliable and a satisfying result for both surgeons and patients.