AimsNeuropilin‐1 (NRP1) and neuropilin‐2 (NRP2) are transmembrane glycoproteins which interact with vascular endothelial growth factor (VEGF) to prevent tumour cell apoptosis and regulate angiogenesis. However, the precise role of NRP1 and NRP2 in the adenoma–carcinoma sequence (ACS) of colorectal cancer remains unclear, and we aimed to determine this in surgical specimens comprising the ACS.Methods and resultsHistological analysis demonstrated that epithelial NRP1 expression increased significantly across the ACS (P = 0.0007), and correlated with microvessel density (MVD; r = 0.505, P = 0.0003) and weakly with VEGF (r = 0.251, P = 0.001). In contrast, although NRP2 epithelial expression was increased significantly in all carcinomas (P < 0.002), there was no correlation with MVD, VEGF or NRP1. Furthermore, patients showing coexpression of NRP1 and NRP2 had a potentially worse prognosis than those expressing a single neuropilin or neither one. Although vascular expression of NRP1 increased significantly across the ACS (P = 0.0004) and correlated with MVD (r = 0.361, P = 0.0006), NRP2 vascular expression decreased significantly (P = 0.0001) and showed an inverse correlation with MVD (r=−0.506, P = 0.0001), suggesting differential roles for neuropilins in the angiogenic process during colorectal cancer development.ConclusionsThese data suggest that an increase in NRP1 and NRP2 epithelial/tumour expression, as well as in NRP1 vascular expression, may be associated with disease progression in colorectal cancer.