It is a classic story of two related transcription factors. Oct4 is a potent regulator of pluripotency during early mammalian embryonic development, and is notable for its ability to convert adult somatic cells to pluripotency. The widely expressed Oct1 protein shares significant homology with Oct4, binds to the same sequences, regulates common target genes, and shares common modes of upstream regulation, including the ability to respond to cellular stress. Both proteins are also associated with malignancy, yet Oct1 cannot substitute for Oct4 in the generation of pluripotency. The molecular underpinnings of these phenomena are emerging, as are the consequences for adult stem cells and cancer, and thereby hangs a tale.