The carbon dioxide (CO2) laser in a short-pulsed mode is currently one of the most useful devices in dermatologic practice in the fields of oncology. To evaluate the safety and efficacy of the short-pulsed CO2 laser in the treatment of cutaneous squamous cell carcinoma (SCC) in situ, the clinical improvement of 40 cases SCC in situ treated with the laser was assessed by a retrospective study. Consequently, it was shown that (1) no clinical evidence of recurrences during the follow-up time (3 to 63 months) in 27 cases, (2) lesion recurrence occurred and additional treatments were required in 13 cases, and (3) hypertrophic scarring was complicated in 1 case. Our findings suggested that the short-pulsed CO2 laser can be considered a safe and effective treatment for patients with SCC in situ, offering excellent cosmetic results