While there is considerable evidence that skin carcinogenesis proceeds as a step‐wise series of changes, little evidence is available to indicate that a similar mechanism applies to oral mucosal carcinogenesis. In the current study, a mouse model of mucosal carcinogenesis was used to examine the effects of repeated applications of the phorbol ester phorbol‐12,13‐didecanoate (FDD) following various periods of treatment with the carcinogen 4‐nitroquinoline‐1‐oxide (4NQO). All animals were histologically examined at 50 weeks. Oral epithelial dysplasia was seen in animals treated with 4NQO for as little as 2 weeks, and oral squamous cell carcinomas developed in all animals treated with 4NQO for 12 weeks. In those mice treated with PDD as well, carcinomas developed in mice receiving as little as 2 weeks treatment with 4NQO, and 100% of mice treated with 4NQO for 12 weeks, followed by PDD treatment, developed carcinomas. The results indicate that irreversible changes in the oral mucosa of mice occur relatively early during treatment with 4NQO, and the development of carcinomas can be enhanced with subsequent PDD treatment, giving an indication of staged carcinogenesis in this m