This study was designed to analyse the potential diagnostic value of miR-181b and miR-21 for discriminating hyperplastic polyps (HP) from sessile serrated adenomas (SSA) without cytologic dysplasia. Using real-time polymerase chain reaction expression levels of miR-181b and miR-21 in 18 HPs, 19 SSAs without cytologic dysplasia and 20 normal colonic mucosal specimens were examined. In addition, 20 colorectal cancers specimen were analysed for miR-181b expression. Data were normalised to RNU48 as an internal control. A differential expression of miR-181b and miR-21 was found in HPs, SSAs, and normal colonic mucosa with highest expression levels in SSAs. Levels of miR-181b but not miR-21 differed in HPs and normal mucosa. SSAs exhibited both significantly higher miR-181b levels (up to 2.01-fold; P < 0.001) and miR-21 levels (up to 1.82-fold; P = 0.011) than HPs. In contrast to HPs, SSAs are characterised by high levels of miR-181b and miR-21 expression. However, due to the overlap of values, miR-181b and miR-21 evaluation did not allow discrimination of the two lesions in every case.