Microquantity differential display analysis of gene expression profiles between benign (PNT2) and malignant (PC3M) human prostate cell lines identified the gene encoding ribosomal protein L19 (RPL19) to be overexpressed in the malignant cells. Northern blot hybridization analysis done on a wide range of human cell lines and tissues confirmed the level of RPL19 mRNA to be 5-fold higher in malignant cell lines and 8-fold higher in malignant tissues, when compared with their benign counterparts. Analysis of RPL19 mRNA expression by in situ hybridization revealed a significant increase of RPL19 expression in a substantial number of prostate cancers. All of the eight normal prostatic tissues were unstained (100%). Of 32 benign prostatic hyperplasia (BPH) tissues, 15 (46.9%) were unstained, 9 (28.1%) stained weakly, and 8 (25%) stained moderately. Among 87 carcinomas, only 7 (8.1%) were unstained, whereas 22 (25.2%) stained weakly, 21 (24.1%) stained moderately, and 37 (42.61%) stained strongly. The intensity of staining of the malignant specimens was significantly higher than that of normal and BPH specimens (chi(2): n = 127, P < 0.001). Gleason scores of the carcinomas correlated with RPL19 expression (chi(2): n = 87, P < 0.001). Kaplan-Meier survival analysis confirmed increased RPL19 expression to be highly predictive of shorter patient survival (P < 0.05), revealing RPL19 to be a sensitive predictor of prostate cancer progression. Expression of this protein could be a valuable marker in prostate cancer diagnosis and patient management.