HER2 is a well-known driver of worse outcomes for many types of cancer, including prostate cancer. While HER2 has been previously evaluated in prostate cancer bench studies and clinical trials, there has been a lack of diversity in the experimental designs and protocols. For this reason, it has only recently been reported that Black men with prostate cancer may have a higher prevalence of HER2 overexpression. To thoroughly address health inequities that exist for Black men with prostate cancer, it is critical to utilize diverse biospecimens and enroll diverse study participants into studies that evaluate genetic and molecular contributors to worse prognosis for high-risk populations. In this review, we reconsider the role of HER2 in prostate cancer with an approach that incorporates the effects of race and genetic ancestry.