Potato plants can accumulate a high amount of cadmium (Cd) in the tuber when grown in soils rich in Cd. The molecular mechanisms governing Cd accumulation in the potato plant are poorly understood. Here we performed an RNA-sequencing experiment to identify genes differentially expressed in the leaf and root of potato during early stages of Cd exposure. Results did not identify any significant transcriptional response in leaves under 1 or 5 mg kg −1 Cd after 72 h. However, in the roots we did identify 2,846 genes that were significantly differentially expressed after 72 h between plants grown in 5 mg kg −1 Cd and controls. These included genes involved in photosynthesis and autophagy being up-regulated, and genes involved in intracellular transport being down-regulated. This study is the first report on the transcriptome-wide response of potato to Cd stress, providing insight into the molecular mechanisms involved in the response.