BACKGROUND Few studies have addressed the clinicopathological features of colorectal cancer (CRC) that express programed death-ligand 1 (PD-L1). Various assays and scoring methodologies were used and thus inconsistent results were obtained. In this study, we aimed to investigate the relationship of PD-L1 expression in CRC with various clinicopathological variables using a standardized assay and scoring algorithm. METHODS Tissue microarrays were constructed from 91 random cases of CRC diagnosed at King Hussein Cancer Center (KHCC). Immunohistochemical (IHC) staining using the monoclonal antibody 22C3 was performed. Scoring using the standard "Combined Positive Score" (CPS) method was done. CPS of ≥1 was considered positive. Various clinicopathological features were collected from the medical records of the patients. RESULTS Of the 91 cases, 49 (53.8%) were PD-L1 positive (CPS ≥1). PD-L1 expression was more frequent among moderately differentiated carcinomas (43 of 72 (59.7%) were positive compared to 6 of 19 (31.5%) poorly differentiated cases (P = 0.029)); among node negative cases (21 of 24 (87.5%) N0 cases were PD-L1 positive in contrast to 28 of 67 (41.8%) N1/N2 cases (P = <0.001)); among mucinous subtype (12 of 15 (80%) of cases (P = 0.02)); and among mismatch repair deficient (dMMR) (16 of 16 (100%) versus 11 of 30 (36.6%) MMR proficient (P = <0.001)). Age, gender, localization, and T or M stages were not significantly associated with PD-L1 expression. CONCLUSIONS PD-L1 expression in CRC is associated with favorable prognostic features; namely, lower grade, N0, mucinous variant, and dMMR tumors.