The incidence of prostate cancer (PCA) was evaluated in 155 patients with isolated Atypical Small Acinar Proliferation (ASAP) found on initial prostate biopsy, after a medium-term follow-up (40 months) with at least one re-biopsy. Clinical and histological data were analysed. Cancer was detected in 81 of 155 (52.3%). The cancer detection rate was 71.6%, 91.3%, 97.5%, 100% at the 1st re-biopsy, 2nd, 3rd, and 4th rebiopsy respectively. At the uni- and multivariate analyses, prostate volume (≤ 30 cc), transition zone volume (≤ 10 cc), small core length at the initial biopsy (≤ 10 mm) and few number of cores at initial biopsy (≤ 8) are predictive of cancer. Furthermore, tumour characteristics on the whole surgical specimens was assessed in 30 men: 13 of 30 (43 %) had clinically relevant cancer (volume > 0.5 ml or/and Gleason score ≥ 7, or pT3). Most of relevant cancers were detected in the distal apex, anterior gland and midline. These anatomical sites could be under-sampled at the initial biopsy using the transrectal approach. Our data suggest that follow-up biopsy is recommended in all cases of isolated ASAP detected after biopsy using endfire transrectal probe. The re-biopsy strategy should increase the number of cores (or a saturation biopsy), focusing on area of ASAP in the initial biopsy, but also including the under-sampled areas (anterior gland, distal apex and midline) to detect clinically relevant cancers.