The invention provides an improved directed complementation method for generating a conditionally tumorigenic mouse cell. In a directed complementation method, the tumorigenicity of a conditionally tumorigenic mouse cell depends on either the expression of an inducible recombinant oncogene or the expression of a recombinant gene of interest that functionally complements an uninduced recombinant oncogene. The invention provides a method of producing a tumorigenic mouse cell containing an uninduced oncogene, a recombinant gene of interest that functionally complements the uninduced oncogene, and a Cre-ER system capable of excising the recombinant gene of interest. When the Cre-ER system is activated, the recombinant gene of interest is excised. From the effect on the mouse cell it is possible to determine whether the recombinant gene of interest is a tumor maintenance gene.