Colorectal adenocarcinoma constitutes the most frequent form of colorectal cancer and a serious cause of cancer-related deaths. The expression of multiple miRNAs, including miR-224, is deregulated in colorectal adenocarcinoma. The aim of this study was the investigation of the prognostic value of miR-224 in colorectal adenocarcinoma. For this purpose, total RNA was isolated from 115 colorectal adenocarcinomas and 66 adjacent non-cancer mucosae. Total RNA (2 µg) was polyadenylated and reverse transcribed. A quantitative PCR method based on SYBR-Green chemistry was developed and applied for the quantification of miR-224 levels, followed by extensive biostatistical analysis. miR-224 levels in malignant colorectal adenocarcinomas ranged between 1.81 and 187.75 RQU (miR-224 copies/1,000 SNORD48 copies) with a median of 34.27, and were significantly elevated, compared to miR-224 levels in adjacent non-cancer mucosae (p<0.001). Enhanced miR-224 expression constitutes a rather strong prognosticator in colorectal adenocarcinoma, predicting short-term relapse and poor overall survival in these patients (p=0.012 and p=0.005, respectively), independent of established clinicopathological parameters. In conclusion, miR-224 is significantly upregulated in malignant colorectal tumors compared to adjacent non-cancer mucosae, and its enhanced expression constitutes an independent predictor of short-term relapse and poor overall survival in colorectal adenocarcinoma patients.