Prostate cancer (PC) remains a cause of death worldwide. Here we investigate whether a single microfocus of PC at the biopsy (graded as Gleason 6 or less, ≤5% occupancy) and the PSA <10 ng/mL can define the archetype of low-risk prostate disease. 4500 consecutive patients were enrolled. Among them, 134 patients with a single micro-focus of PC were followed up, and the parameters influencing the biochemical relapse (BR) were analysed. Out of 134 patients, 94 had clinically significant disease, specifically in 74.26% of the patients with PSA <10 ng/mL. Positive surgical margins and the extracapsular invasion were found in 29.1% and 51.4% patients, respectively. BR was observed in 29.6% of the patients. Cox regression evidenced a correlation between the BR and Gleason grade at the retropubic radical prostatectomy (RRP), capsular invasion, and the presence of positive surgical margins. Multivariate regression analysis showed a statistically significant correlation between the presence of surgical margins at the RRP and BR. Considering a single micro-focus of PC at the biopsy and PSA serum level <10 ng/mL, clinically significant disease was found in 74.26% patients and only positive surgical margins are useful for predicting the BR
