An intriguing study recently identified sphingosine-1-phosphate receptor 1 (S1PR1) as a key element involved in the persistent activation of signal transducer and activator of transcription-3 (STAT3) both in tumor cells and the tumor microenvironment in animal models of melanoma (B16) and bladder cancer (MB49). The gene discussed is STAT3; the disease is urinary bladder carcinoma.