Objective: Detection of C4d is crucial for diagnosing antibody mediated rejection, yet formal reproducibility studies are limited. Method: We conducted an international multi-center trial to assess the reproducibility for C4d immunohistochemistry on paraffin-sections. A tissue microarray (TMA) was constructed comprising 44 kidney allograft specimens representing negative, focal, and diffuse C4d positive cases. Participants stained the TMA slides, evaluated their stains and entered their scores online. Stained slides were returned for centralized panel scoring. Weighted kappa statistics were used to determine reproducibility. Results: Inter-institutional reproducibility, i.e. the product from variability between observers and staining methods was low (mean kappa 0.17). Inter-observer reproducibility was fair (kappa 0.39), while inter-laboratory reproducibility was moderate (kappa 0.49). Inter-observer reproducibility could be significantly improved by omitting the Banff C4d grading schema and only considering +/− calls (kappa 0.60). Scoring only C4d+/− inter-laboratory reproducibility improved considerably (kappa 0.78). Higher dilutions of the primary antibody were associated with worse reproducibility. Fixation <1 h or fixation in ethanol had significant negative impact on inter-laboratory reproducibility. Conclusion: C4d results reported from paraffin section are highly variable between institutions. Simplification of the grading schema would improve reproducibility between observers. Technical reproducibility between laboratories is acceptable but could further be improved by standardizing protocols. Objective: Heparanase is a predominant mammalian enzyme that cleaves heparan sulfate, the key polysaccharide found in the basement membranes and at cell surface.