With the recent sequencing of its entire genome, the yeast Saccharomyces cerevisiae has gained considerable interest in the field of anticancer research. The genetic properties of the yeast allow easy selection of a variety of mutants, as their related phenotypes provide valuable information on anticancer drugs effects in vivo. Moreover, the yeast has been extensively studied as a model system to decipher basic cellular processes that are well conserved from yeast to human and implicated in cancer establishment and progression. We discuss the advantages of Saccharomyces cerevisiae for investigating the metabolism of pyrimidines, a major target for anticancer chemotherapy. We also emphasize the links between basic science in the pyrimidine metabolism and new anticancer antimetabolites as well as future prospects in this field.