Background: Elevated levels of arsenic in drinking water in Cambodia were first identified in 1999. The first cases of suspected arsenicosis were identified by the WHO in 2002, and the first laboratory confirmed cases were found in 2006. Objective: Present three patients with ulcerating tumors of the legs who came from two different districts in Cambodia. Results: Cutaneous lesions characteristic of chronic arsenicosis were exhibited, and squamous cell carcinomas requiring amputation had developed. The clinical features of chronic arsenicosis and its surgical management were examined, in addition to its impact in Cambodia and current preventive strategies Conclusion: There will be an increased incidence of these problems in the future. Medical practitioners in the Mekong River Basin should be aware of them, so as to recognize them early, and treat them appropriately.