Emerging observations emphasize a distinct biology of prostate cancer among men of different ethnicities and races, as demonstrated by remarkable differences in the frequency of ERG oncogenic activation, one of the most common and widely studied prostate cancer driver genes. Worldwide assessment of ERG alterations frequencies show consistent trends, with men of European ancestry having the highest rates of alteration and men of African or Asian ancestries having considerably lower alteration rates. However, data must be interpreted cautiously, owing to variations in assay platforms and specimen types, as well as ethnic and geographical classifications. Many opportunities and challenges remain in assessing cancer-associated molecular alterations at a global level, and these need to be addressed in order to realize the true potential of precision medicine for all cancer patients.