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Phaeocystis globosa forms dense, monospecific blooms in temperate, northern waters. Blooms are usually dominated by the colonial morphotype-nonflagellated cells embedded in a secreted mucilaginous mass. Colonial Phaeocystis blooms significantly affect food-web structure and function and negatively impact fisheries and aquaculture, but factors regulating colony formation remain enigmatic. Destructive P. globosa blooms have been reported in tropical and subtropical regions more recently and warm-water blooms could become more common with continued climate change and coastal eutrophication. We therefore assessed genetic pathways associated with colony formation by investigating differential gene expression between colonial and solitary cells of a warm-water P. globosa strain. Our results illustrate a transcriptional shift in colonial cells with most of the differentially expressed genes downregulated, supporting a reallocation of resources associated with forming and maintaining colonies. Dimethylsulfide and acrylate production and pathogen interaction pathways were upregulated in colonial cells, suggesting a defensive role for producing colonies. We identify several protein kinase signaling pathways that may influence the transition between morphotypes, providing targets for future research into factors affecting colony formation. This study provides novel insights into genetic mechanisms involved in Phaeocystis colony formation and provides new evidence supporting a defensive role for Phaeocystis colonies.