BACKGROUND: Most molecular techniques currently require fresh frozen tumor tissue, which in the case of prostatectomy specimen is a challenge to obtain for a variety of intrinsic reasons. Prostate cancers are usually located in the organ periphery and hence meticulous attention has to be paid to the relation between the tumor and the surgical margin. In this article we describe a new technique that allows to obtain fresh frozen tumor material in rather large quantities and without jeopardizing diagnostic accuracy. METHOD: An inner triangle, representing roughly 50% of the entire prostate tissue, is removed from native prostatectomy specimen and cryopreserved, leaving the periphery of the organ for routine histomorphological analysis. We have validated the technique using a series of 180 archived radical prostatectomy specimen that had been studied by histology in their entirety, as well as 42 prostatectomy specimen worked-up by the new technique. RESULTS: The described technique is effective, yielding frozen tumor tissue in 84.2% of unilateral (<or=pT2b) and in 91.8% of bilateral (pT2c) carcinomas. The number of tumor containing tissue blocks ranged from 1 to 7 blocks per carcinoma (mean 5.6 +/- 3.2). The remaining peripheral tissue portion subjected to histological analysis allowed to estimate total tumor volume with a high degree to confidentiality (r(2) >or= 0.90 by linear regression analysis). The number of blocks to be routinely examined for each prostatectomy specimen is significantly reduced, thus saving costs without loss of diagnostic accuracy. CONCLUSION: The described technique for prostate cancer cryoconservtion is feasible, highly standardized, effective, safe, and economic.