Lipofuscin, known as the "wear and tear" pigment, is seen in cells undergoing regressive changes, the seminal vesicles and the ejaculatory ducts. It is also present in prostatic adenocarcinoma. The purpose of this study is to evaluate the prognostic significance of lipofuscin in prostatic adenocarcinoma. Lipofuscin was evaluated in 736 hematoxylin-eosin-stained slides from 60 conventional and whole-mounted consecutive radical prostatectomies from December 1996 to February 2002. The adenocarcinoma cases were divided into lipofuscin-positive group and lipofuscin-negative group. The Gleason score and pathologic stage were compared between the 2 groups. Percentage of cells positive for p53 and MIB-1 was also compared. Lipofuscin pigment was found in 17 (31%) of 60 prostatic adenocarcinomas as random, sparse, fine, yellow-brown intracytoplasmic granules staining positive for cathepsin D and negative for S-100 protein. Using logistic regression to exclude age as a confounding factor, lower Gleason scores and pathologic stages were demonstrated in the lipofuscin-positive group. There was also a significant difference between the 2 groups in tumor volume, degree of capsular invasion, and positive margins. The difference in seminal vesicle invasion and vascular invasion between the 2 groups was not statistically significant. Lipofuscin in prostatic adenocarcinoma correlates with both lower Gleason score and pathologic stage. Lipofuscin probably indicates slow cellular turnover as suggested by the low proliferation rate and p53 expression. The value of lipofuscin in biopsy as a predictor separating aggressive from indolent disease needs further investigation.