Despite the near ubiquitous use of therapies targeting the androgen receptor (AR) axis in prostate cancer, there remains, at this date, no integrated diagnostic test designed to select and individualize patients for hormonal-based treatments. From the article by Chmelar and coauthors, we may have a glimpse as to a way forward to the development of a test that can successfully guide the use of androgen ablation therapy. By turning our attention away from the AR gene and protein itself and focusing on coregulators of the AR pathway we may have a new opportunity to develop a single or group of slide-based tests designed to assess AR pathway status on the needle biopsy of a newly diagnosed prostate cancer patient and predict the clinical benefit of total androgen blockade treatment strategies.