Carthamus tinctorius L. (safflower) is being evaluated as a crop for the production of plant-made pharmaceuticals using an oleosin fusion protein system. We evaluated the potential for transgenic gene flow from C. tinctorius to wild or weedy relatives in western Canada. Cytogenetic and phylogenetic studies with most of the species of Carthamus have demonstrated that cultivated C. tinctorius has the ability to hybridize with at least six wild or weedy relatives worldwide. Of the four naturalized wild relatives in the New World, only two, C. oxyacanthus and C. creticus, have successfully been crossed with C. tinctorius to produce fertile hybrids. Data from artificial crosses resulting in fertile offspring indicate the biological potential of a hybridization event, but only if the species are temporally and spatially sympatric can this occur. Based on the New World distribution of C. oxyacanthus and C. creticus we predict that hybridization with transgenic C. tinctorius could occur in some areas of Argentina, Chile and localities within several states in the United States including California, Florida, Illinois, Kansas, New Mexico, Ohio, Oklahoma, Oregon, Utah, and Texas. Locations in the New World where wild species of Carthamus have not been naturalized may provide biologically isolated locations for the cultivation of a transgenic safflower crop.