Mammary tumors in the GR strain are caused by a dominant locus containing an endogenous mouse mammary tumor provirus. Expression of this locus results in high virus titers, inducing tumors that progress from a hormone-dependent to a hormone-independent tumor state. We previously studied the activation of the Wnt-1 and int-2 oncogenes in several series of transplanted GR tumors and found that hormone-dependent early passages are generally oligoclonal for proviral integration at these genes. We have now re-examined several such tumor series for activation of other Wnt genes. In one series, the transition to hormone-independent growth was marked by the loss of the oligoclonal genotype and outgrowth of a hormone-independent cell population, clonal for the activation of Wnt-3. We show two examples of series of transplanted tumors that in later hormone-independent passages contain an amplified and overexpressed Wnt-2 gene, a novel mode of activation of these genes.