Taking into consideration the increasing evidence regarding the critical role that CSCs play in both tumor initiation and tumor resistance and relapse following chemo–radiotherapy, the aim of the present pilot study was to investigate possible correlations between the clinicopathological characteristics of CRC patients and the CD133, CD166, and CD44 gene expression patterns, in order to provide insight into additional methods for patient stratification, followed by the development of targeted therapeutic strategies. This evidence concerns the gene PROM1 and neoplasm.