The identification of the TMPRSS2: ERG fusion in prostate cancer suggests that distinct molecular subtypes may define risk for disease progression. In surgical series, TMPRSS2: ERG fusion was identified in 50% of the tumors. Here, we report on a population-based cohort of men with localized prostate cancers followed by expectant (watchful waiting) therapy with 15%(17/111) TMPRSS2: ERG fusion. We identified a statistically significant association between TMPRSS2: ERG fusion and prostate cancer specific death (cumulative incidence ratio= 2.7, P< 0.01, 95% confidence interval= 1.3–5.8). Quantitative reverse-transcription–polymerase chain reaction demonstrated high estrogen-regulated gene (ERG) expression to be associated with TMPRSS2: ERG fusion (P< 0.005). These data suggest that TMPRSS2: ERG fusion prostate cancers may have a more aggressive phenotype, possibly mediated through increased ERG expression.