Corals are marine invertebrates that are facing life-threatening environmental stressors due to climate change. Polyploidy can, in such cases, be an important source of variation and adaptation in corals and other species. Polyploidy is the genomic condition wherein the cells of a normally diploid organism have more than one pair of chromosomes. Pocillopora acuta, also known as the cauliflower coral, is a brooding coral that can also reproduce asexually. It is a stress-sensitive coral, which means it shows clear physiological changes in response to environmental stressors like temperature, salinity, and pH. In this study, about 60% of the stony coral Pocillopora acuta samples collected from Kāneʻohe Bay, Oahu, HI, were triploid. The aim of this study was to identify the differences in gene expression patterns between triploid cluster 1 (T1), triploid cluster 2 (T2), and diploid samples (D) of P. acuta. Pairwise comparisons were carried out between all categories: T1 vs. D, T2 vs. D, and T1 vs. T2. While there were a large number of genes exhibiting similar expression patterns in both triploid clusters, many genes were differentially regulated in T1 when compared to T2. This result provides evidence suggesting that the two triploid lineages originated from separate triploidization events in Kāneʻohe Bay. The differentially expressed genes shared between these two triploid lineages, when compared to the diploid coral lineage, suggests changes in cellular physiology as a result of polyploidization. Functional analysis of the P. acuta genes can provide deeper insight into the specific, differentially regulated molecular functions and biological processes in triploids when compared to diploid P. acuta. Future studies involving comparative functional enrichment analysis with more triploid and diploid samples of P. acuta will provide more insight into events that caused triploidization and the coral’s response to environmental stressors.