Prostate cancer is the most common cancer and the second most common cause of cancer-related death in men. The standard treatment is androgen deprivation therapy (castration), but prostate cancer becomes resistant to this treatment over time. Targeting the androgen receptor seems logical but has had little effect on patient survival so far. Intriguingly, a chemical related to estrogen, 4-hydroxyestradiol (4-OHE2), also promotes cancer occurrence and progression. A recent study examined the role of 4-OHE2 in castration-resistant prostate cancer (CRPC) cells. The protein CYP1B1 is involved in the production of 4-OHE2, and CYP1B1 was found to be elevated in CRPC cells. In addition, 4-OHE2 promoted ERα transcriptional activity in CRPC cells. 4-OHE2 promoted tumor formation through the IL6-STAT3 pathway, which sends inflammatory signals important in many cancers. Targeting 4-OHE2 production with new treatments could cut this signal off at the source, potentially leading to increased survival and quality of life for patients with prostate cancer.