Nectin‐4 is an E‐cadherin‐based adherens junction protein of normal epithelial cells, as well as a potent mediator of anchorage‐independent cancer colony formation. It is considered a tumour‐associated histological and serological marker in various human cancers. The transcription factor p63 is a basal cell marker in the normal prostate, involved in cell adhesion, as well as in the formation and survival of circulating tumour cell clusters. The aim of this study was to evaluate Nectin‐4 and p63 immunohistochemical expression in 42 canine prostate tissues including 2 normal prostates, 10 benign prostatic hyperplasias (BPHs), 30 prostatic carcinomas (PCs), 1 pulmonary and 1 lymph node metastasis. From normal to neoplastic tissues, Nectin‐4 showed a progressive switching from membranous (m‐Nectin‐4) to cytoplasmic (c‐Nectin‐4), regardless of the histological subtypes, except for lack of expression in solid PCs. Metastatic cells exhibited both strong membranous and cytoplasmic positivity. c‐Nectin‐4 expression was significantly (P < 0.0001) increased in PCs/metastasis compared to BPHs cases and a decrease (P < 0.05) of nuclear p63 immunostaining was also detected in the two groups. Furthermore, data showed a significant association (P < 0.05) between p63 and m‐Nectin‐4 distribution, although their colocalization was detected only in scattered cells by double immunofluorescence. Our results suggest the involvement of m‐Nectin‐4 in canine prostate tumourigenesis and metastatic potential, while the exact role of c‐Nectin‐4 expression detectable in primary PCs requires further investigations.