Formalin-fixed paraffin-embedded (FFPE) tissues stored in Departments of Pathology have become valuable sources of material for both diagnostic and research purposes. Obtaining nucleic acids from this material may be challenging, especially after storage for several years. The present study was aimed at evaluating DNA degradation over time by comparing the quality of DNA obtained in 2002 with the quality of DNA obtained in 2010 from the same paraffin blocks. The DNA obtained after several years from FFPE tissues was, in the majority of cases, of lower quality in terms of amplifiable length of nuclear DNA by PCR, and only a minority of them are still equally amplifiable. For this reason, if it is suspected that a molecular analysis may be necessary in the future, it would be important to obtain nucleic acids shortly after the diagnostic process is over or, when possible, to keep frozen samples at the institutional biorepository.