The receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a transmembrane protein that belongs to a conserved family of tyrosine kinase receptors involved in several functional processes. ROR2 is overexpressed in various types of solid tumors; however, the expression of ROR2, as well as its functional and prognostic significance has yet to be evaluated in colorectal cancer (CRC). In this study, one-step quantitative reverse transcription-polymerase chain reaction and immunohistochemical analysis using tissue microarrays were used to evaluate ROR2 expression in CRC and to investigate the association between ROR2 expression and patient prognosis. We observed that the expression of ROR2 mRNA and protein was significantly higher in CRC specimens compared with normal, tumor-adjacent tissues (both p < 0.05). Cytoplasmic ROR2 expression was related to TNM stage (p = 0.041) and lymph node metastasis (N) (p = 0.015). Kaplan-Meier and multivariate analyses suggested that high cytoplasmic ROR2 expression (p = 0.001), poor tumor differentiation (p = 0.001), and advanced TNM stage (p = 0.001) and high pre-operative CEA level (p < 0.001) were significantly associated with unfavorable survival of CRC patients. These results suggest that ROR2 expression is correlated with malignant attributes of CRC and may serve as an indicator for poor prognosis in patients with CRC. (C) 2014 Elsevier Inc. All rights reserved.