Although chromosomal duplications are often deleterious, in some cases they enhance cells' abilities to tolerate specific genetic or environmental challenges. Identifying the genes that cause particular chromosomal duplications to confer these conditionally beneficial effects can improve our understanding of the genetic and molecular mechanisms that enable certain aneuploidies to persist in cell populations and contribute to disease and evolution. Here, we perform a screen for spontaneous mutations that improve the tolerance of haploid Saccharomyces cerevisiae to hydrogen peroxide. Chromosome IV duplication is the most frequent mutation, as well as the only change in chromosomal copy number, seen in the screen. Using a genetic mapping strategy that involves systematically deleting segments of a duplicated chromosome, we show that the Chromosome IV duplication's effect is largely due to the generation of a second copy of the stress-inducible cytoplasmic thioredoxin peroxidase TSA2. This finding is consistent with a growing literature indicating that the conditionally beneficial effects of chromosomal duplications tend to reflect the contributions of small numbers of genes that enhance tolerance to specific stresses when their copy number is increased.