The novel tumor suppressor Pdcd4 inhibits neoplastic transformation, tumor progression and translation. Furthermore, we and others have recently shown that Pdcd4 suppresses invasion and intravasation, at least in part by suppressing expression of the invasion-related urokinase receptor (u-PAR) gene via the transcription factors Sp1/Sp3. Nevertheless, relatively little is known about mechanisms that regulate Pdcd4 expression in cancer. MicroRNAs (miRNAs) have been recently discovered and shown to be naturally occurring non-coding RNAs that control gene expression via specific sites within the 3'UTR of target miRNAs. This short review will focus on our recent finding that the microRNA miR-21 posttranscriptionally regulates Pdcd4, as well as invasion, intravasation, and metastasis. Furthermore, we will review the first translational and clinical results concerning the prognostic value of Pdcd4, in particular our own data that show Pdcd4 to be a novel and independent prognostic factor in colorectal cancer, and a potential supportive diagnostic tool for discriminating normal colonic tissues from benign adenomas and colorectal carcinomas.