The present article explores the intellectual history of an imaginary substance called “human yellow.” It first appears in a passage of the Chinese Commentary to the Mahāvairocana Sūtra as a magical substance found in the human heart, which is the favourite food of ogresses of the category of ḍākinīs: these horrible female demons eat it, gaining from it their magical power. This passage stimulated the interest of Japanese esoteric monks, who speculated on “human yellow” in various ways. “Human yellow” was also imagined as one of the main attributes held by the vidyārāja (King of Wisdom) Aizen Myōō and thought to be a kind of biological substance from which life originates. This article is composed of two parts: one on the origin of the complex speculation on this substance; and the other on some of the final developments of such speculation, in which one can recognise interesting themes related to reproduction symbolism. Specifically, we will analyse the “skull ritual” of a particular religious movement described in the record entitled Juhōyōjinshū (1268), which was mistakenly identified as a Tachikawa-ryū ritual in later historiography. This examination shows that “human yellow,” imagined as the essence of life, turned out to be a key concept from which this skull ritual generated. Smearing the skull with sexual fluids, in which “human yellow” was believed to exist, turned it into a kind of philosopher’s stone, an almighty magical, and living, object. The translation and annotation of some lengthier original texts are provided in the Appendices.