The transcription factor heat shock factor 1 (HSF1) is the master regulator of the heat shock response. It is crucial for cell homeostasis and implicated in aging, neurodegenerative disease and cancer. Although induction by HSF1 of the expression of molecular chaperones and other regulators of protein quality control, both folding and degradation, is well established, the precise and detailed transcriptional network that HSF1 regulates in cancer is poorly understood. An important new study identifies an HSF1-regulated transcriptional program in highly malignant cells that is surprisingly distinct from the traditional heat shock response. The results have significant implications for our molecular understanding of cancer and the development of new therapies.