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BACKGROUND: Programmed cell death 1 (PD 1) receptor triggering by PD ligand 1 (PD L1) inhibits T cell activation. PD L1 expression was detected in different malignancies and associated with poor prognosis. Therapeutic antibodies inhibiting PD 1/PD L1 interaction have been developed. MATERIALS AND METHODS: A tissue microarray (n=1491) including healthy colon mucosa and clinically annotated colorectal cancer (CRC) specimens was stained with two PD L1 specific antibody preparations. Surgically excised CRC specimens were enzymatically digested and analysed for cluster of differentiation 8 (CD8) and PD 1 expression. RESULTS: Strong PD L1 expression was observed in 37 of mismatch repair (MMR) proficient and in 29 of MMR deficient CRC. In MMR proficient CRC strong PD L1 expression correlated with infiltration by CD8+ lymphocytes (P=0.0001) which did not express PD 1. In univariate analysis strong PD L1 expression in MMR proficient CRC was significantly associated with early T stage absence of lymph node metastases lower tumour grade absence of vascular invasion and significantly improved survival in training (P=0.0001) and validation (P=0.03) sets. A similar trend (P=0.052) was also detectable in multivariate analysis including age sex T stage N stage tumour grade vascular invasion invasive margin and MMR status. Interestingly programmed death receptor ligand 1 (PDL 1) and interferon (IFN) ? gene expression as detected by quantitative reverse transcriptase polymerase chain reaction (RT PCR) in fresh frozen CRC specimens (n=42) were found to be significantly associated (r=0.33 P=0.03). CONCLUSION: PD L1 expression is paradoxically associated with improved survival in MMR proficient CRC.