Cannabinoids are a diverse group of compounds with increasing promise in a broad range of pharmaceutical and commercial applications. While trans-Ä9-tetrahydrocannabinol (Ä9-THC) and cannabidiol (CBD) are the best known and most widely used, over a hundred other rare cannabinoids are present in low abundance in the Cannabis sativa plant. While current research is underway to elucidate the bioactivities of these rare cannabinoids, they have drawn much less attention than CBD and Ä9-THC as they are more challenging and less sustainable to extract from plant material. Recently, yeast-based biomanufacturing platforms have emerged to provide researchers and product developers with highly-pure, sustainable, and reliable sources of rare cannabinoids, opening up a whole new family of molecules for commercialization. Two specific cannabinoids, cannabigerolic acid (CBGA) and cannabichromene (CBC) are of particular interest due to their central role in cannabinoid biosynthesis. CBGA is the precursor cannabinoid to many other cannabinoids, and CBC is one of the rare cannabinoids in the mature Cannabis plant. To better understand the potential applications of these two unique cannabinoids, we performed transcriptomic analysis on CBGA- or CBC-treated epidermal or dermal skin cells. We found that each has a distinct transcriptomic response: CBGA may play a role in wound repair and hyperpigmentation, while CBC may induce an anti-microbial immune response. These results lay the foundation for applying CBGA and CBC in skincare formulations and providing consumers with a new suite of products.