BACKGROUND: Fordyce spots are heterotopic sebaceous glands that can be located at the lips' vermilion or the oral mucosa. Although this is considered a rather common disorder, a treatment for this condition that sometimes affects patients from only a cosmetic viewpoint has not yet been described. OBJECTIVE: To evaluate CO2 superpulsed laser treatment in two subjects with Fordyce spots. METHODS: Two patients with papules and yellowish plaques at the upper lip corresponding to Fordyce spots were treated with coherent Ambulase CO2 superpulsed laser (Coherent Medical, Palo Alto, CA); after informed consent was obtained, two to three passes were performed in one session using 2 and 4 W and a spot size of 2 mm. RESULTS: Complete re-epithelization was observed 2 weeks later with no residual Fordyce papules in the treated area and no side effects. CONCLUSION: Our findings suggest that CO2 superpulsed laser can be considered a safe and effective treatment for patients with Fordyce spots, offering excellent cosmetic results.