The Saccharomyces cerevisiae genome has been studied extensively since it was first sequenced 20 years ago. A number of open-reading frames in this genome, are still classified as “dubious” including those that overlap open-reading frames known to encode functional proteins. We reexamined whether this status is still warranted given the large increase in data from numerous sources. These data include genomic information from other members of the Saccharomyces clade and transcriptome information from S. cerevisiae grown under a number of different conditions. Using genomic data we first examined the conservation of these ORFs compared to other members of the clade. Second, we examined existing data from tiling microarray and RNA-seq experiments. Our data show that these ORFs are in fact conserved and many of them are differentially expressed, suggesting a functional role.