Signal transducer and activator of transcription 3 (STAT3) has well-characterized oncogenic activities in various cancers. However, Jacqueline Bromberg, David Lyden and colleagues found that, in clinical thyroid cancer samples, levels of phosphorylated (active) STAT3 negatively correlated with tumour size and metastasis. Furthermore, loss of STAT3 expression increased thyroid cell tumorigenicity in vivo in both xenograft and orthotopic mouse models. This study highlights a possible tumour suppressor role for STAT3 in thyroid cancer, which may involve a STAT3-regulated metabolic switch.