Abstract We investigate the determinability of model parameters for a two-stage cancer model, using as an example chemically induced skin cancer in mice. When the time course of the papilloma number and cancer rate are known, the rate of creation of initiated cells and their net-growth rate can be uniquely determined. These two high-level parameters are sufficient to uniquely simulate the experimental papilloma data. However, the mitotic and death rates of initiated and transformed cells cannot be determined from the available experimental data. The rate of creation of transformed cells and their net-growth rate cannot be determined independently. Thus, although the deterministic two-stage cancer model can simulate the kinetics of papilloma formation and skin cancer data, many of the basic underlying biological parameters (i.e., mitotic and death rates) cannot be uniquely determined from the usually available biological data.