As a pioneering work in the field of domestication of Pyrenacantha volubilis Wight, an anti-cancer drug (camptothecin) yielding plant, this study identifies superior seed sources of southern peninsular India for various parameters related to its growth and yield. The experiment was set up following the common garden experiment protocol in Completely Randomised Design. Laboratory extraction of camptothecin from whole seeds was carried out using High Performance Liquid Chromatography. Whereas seeds from Kizhoor population were the heaviest (test weight of 171.5 g), seedlings obtained by sowing the seeds from Villiampakkam population performed better in terms of total yield per plant (5.25 g dry weight) as well as total camptothecin yield per hectare (223.125 g). Almost three times variation was observed in the experiment between the poorest and the best performing populations. We attempt to discuss the potential for domestication, large-scale planting and sustainable harvesting of this promising and versatile new cash crop.